Unlocking The Power Of The Immune System To Get Ahead Of Hepatitis B
The liver performs over 500 tasks each day that help keep us alive and healthy and has the unique ability to regenerate itself when it becomes damaged. Yet some peoples livers harbour an infection that could impact liver function and may cause the organ to fail: hepatitis B.
Hepatitis B virus infection is caused by a virus that is spread through blood and bodily fluids and localises in the liver. Estimates suggest that one in every three people has been exposed to the hepatitis B virus at some point in their lives, but many of these people will develop natural immunity to the infection. However, up to 10% of adults and nearly all babies infected via their mother during birth will experience an inadequate immune response to the virus causing them to develop chronic, or lifelong, hepatitis B virus infection. The World Health Organization estimates that over 296 million people live with chronic hepatitis B virus infection worldwide, making it a major global health problem.
At GSK, we have been working hard to get ahead of hepatitis B for decades. Vaccines that help prevent hepatitis B virus infection now exist, and antiviral therapies are available to help control the infection. Yet the burden for many remains. We are using our expertise to advance research to help reduce this burden.
Mechanisms Of Action Of Na And Ifn
NAs inhibit reverse transcription of pregenomic RNA and synthesis of HBV DNA in the cytoplasm and have no direct effect on cccDNA. IFN has both antiviral and immunomodulatory activities, although the precise mechanisms of action remain unclear. Recent studies suggest that IFN may enhance cccDNA degradation and exert epigenetic modification of cccDNA transcription, explaining its greater effect on viral protein production and higher rates of HBeAg and hepatitis B surface antigen loss compared to NAs.
Barriers To Eliminating Hbv
Persistence of cccDNA and its ability to self-replenish and the lack of direct effects of current therapies on cccDNA account for the difficulty in eliminating cccDNA. There are additional barriers to eliminating HBV. HBV DNA can be integrated into the host genome. Although integrated HBV DNA is often rearranged and/or partially deleted and there is no evidence that it supports the full cycle of HBV replication, recent studies suggest that integrated HBV DNA can be sufficiently intact to support translation of viral proteins, e.g., HBsAg. Elimination of integrated HBV DNA will likely require the removal of hepatocytes that harbor these DNA. Control of infections generally requires elimination of the infectious organisms coupled with activation of specific immune responses. Whereas patients who recover from acute HBV infection display rigorous immune responses to multiple HBV epitopes, patients with chronic HBV infection manifest weak immune responses to very few HBV epitopes.
Read Also: Signs You Have Hepatitis C
Hepatitis B Causes And Risk Factors
Itâs caused by the hepatitis B virus, and it can spread from person to person in certain ways. You can spread the hepatitis B virus even if you donât feel sick.
The most common ways to get hepatitis B include:
- Sex. You can get it if you have unprotected sex with someone who has it and your partnerâs blood, saliva, , or vaginal secretions enter your body.
- Sharing needles. The virus spreads easily via needles and syringes contaminated with infected blood.
- Accidental needle sticks.Health care workers and anyone else who comes in contact with human blood can get it this way.
- Mother to child.Pregnant women with hepatitis B can pass it to their babies during childbirth. But thereâs a vaccine to prevent newborns from becoming infected.
Treatment For The Acute Phase
Most adult who become infected with hepatitis B do not require any specific treatment as they usually recover completely within a few weeks or months. On very rare occassions, hospital admission for acute hepatitis may be neccessary, and in a very small minority, anti-viral treatment may be indicated. No treatment can prevent acute hepatitis B from becoming chronic. To be confident that the infection has resolved, you should be re-tested six months after the initial positive test.
Read Also: How Many Shot For Hepatitis B
Treatment For Chronic Infection
Not all those infected with Hepatitis B require treatment, only those with persistently high levels of the virus in their blood and evidence of the infection affecting the liver. Treatment does not cure hepatitis B, but by suppressing the virus, works to delay or even prevent complications developing, such as liver damage and cirrhosis. A liver specialist will usually advise on when treatment may be beneficial. There are two types of treatment currently given:
New And Current Treatment Options For Hepatitis B
The search for new treatments for hepatitis B has been ongoing for decades. While effective at suppressing the virus, current treatments, which include antivirals, cannot eliminate it from the liver.
Hepatitis B is a liver infection that results from the hepatitis B virus. People acquire it through contact with the bodily fluids of someone with the virus. The liver cleanses the body of waste, and the disruption to its processes can make a person seriously ill.
This article will outline the current treatment options for HBV. It will also discuss new treatments in development that may lead to a cure for HBV.
Initial infection with HBV is an acute infection. Most healthy people with infection with this virus will not have symptoms and can shed the virus easily. If tests show that a person still has the virus 6 months after contracting it, they have a chronic, long-term infection. Doctors use blood tests to diagnose and monitor the condition.
Treatment whether a person has acute or chronic hepatitis B.
Molecular Mechanisms Of Drug Resistance
Different types of mutations are associated with drug resistance and can emerge during antiviral therapy with nucleoside or nucleotide analogues. Primary mutations typically affect the reverse transcriptase domain of the HBV polymerase, thereby causing steric changes of the polymerase protein that escape the inhibitory effects of the nucleoside analogues . The most relevant hot-spot mutations in the HBV polymerase are displayed in Table 1. However, the polymerase mutants have a dramatically reduced viral replication efficacy in most cases . Secondary compensatory mutations occur in order to restore the viral replication fitness, thereby overcoming deleterious effects of the primary drug-resistant mutations . These mutations are not necessarily located within the enzymatically active sites of the polymerase, but oftentimes stabilize secondary or tertiary viral structures. The eight different HBV genotypes AH partly differ with respect to the position of secondary compensatory mutations and the rate of drug resistance development .
American Association For The Study Of Liver Diseases Recommendations
The 2016 AASLD guidelines for the treatment of chronic hepatitis B as well as select recommendations from the 2018 AASLD guidance update on the prevention, diagnosis, and treatment of chronic hepatitis B are outlined below and in the Guidelines section.
Adults with immune-active chronic hepatitis B infection
Administer antiviral therapy to lower the risk of morbidity and mortality associated with chronic hepatitis B infection.
The recommended initial agent for adults is PEG-IFN, entecavir, or tenofovir.
Adults with immune-tolerant chronic hepatitis B infection
Antiviral therapy is not recommended.
The AASLD suggests obtaining ALT levels at least every 6 months to monitor for potential transition to immune-active or -inactive chronic hepatitis B.
For select patients older than 40 years, the AASLD suggests antiviral therapy in the setting of normal ALT levels, elevated HBV DNA , and significant necroinflammation or fibrosis on liver biopsy specimens.
Adults with HBeAg-positive immune-active chronic hepatitis B who seroconvert to anti-HBe on nucleoside analog therapy
After a period of treatment consolidation , consider discontinuing NA therapy in noncirrhotic HBeAg-positive adults who seroconvert to anti-HBe while on NA treatment. If antiviral therapy is stopped, monitor the patient every 3 months for a minimum of 1 year for recurrent viremia, ALT flares, seroreversion, and clinical decompensation.
Adults with HBeAg-negative immune-active chronic HBV infection
Read Also: Hepatitis C Treatment Guidelines 2017
What Should You Know About Pregnancy And Hepatitis B
A pregnant woman who has hepatitis B can pass the infection to her baby at delivery. This is true for both vaginal and cesarean deliveries.
You should ask your healthcare provider to test you for hepatitis B when you find out you are pregnant. However, while it is important for you and your healthcare provider to know if you do have hepatitis B, the condition should not affect the way that your pregnancy progresses.
If you do test positive, your provider may suggest that you contact another healthcare provider, a liver doctor, who is skilled in managing people with hepatitis B infections. You may have a high viral load and may need treatment during the last 3 months of your pregnancy. A viral load is the term for how much of the infection you have inside of you.
You can prevent your infant from getting hepatitis B infection by making sure that your baby gets the hepatitis B vaccine in the hours after they are born along with the hepatitis B immunoglobulin. These two shots are given in two different locations on the baby. They are the first shots needed.
Depending on the type of vaccine used, two or three more doses must be given, usually when the baby is 1 month old and then 6 months old, with the last by the time the baby is 1 year old. It is critical that all newborns get the hepatitis B vaccination, but even more important if you have hepatitis B yourself.
Is There A Cure For Chronic Hepatitis B
Currently, there is no complete cure for hepatitis B. But when managed properly, those living with the virus can expect to live a normal life. Maintaining a healthy diet and avoiding alcoholic beverages and tobacco products are crucial components in managing the disease.
You should also visit a doctor familiar with hepatitis B at least annuallythough twice a year might be best to monitor your liver through blood tests and medical imaging. As with most diseases, detecting it early leads to a better outcome. If youre exposed to the virus, you should get an antibody injection within 12 hours of exposure.
You May Like: How Do You Get Chronic Hepatitis B
Developing A Cure For Chronic Hepatitis B Requires A Fresh Approach
Illustration of hepatitis B virus.Credit: Urfinguss/Getty Images
Approved treatments for chronic infections of hepatitis B virus are currently limited to two main types: injections of interferon, a substance normally produced by the immune system to fight infections, and nucleoside or nucleotide analogues . NUCs are well-tolerated drugs that can be taken orally to potently suppress virus replication, and are the main therapy for chronic HBV in most countries. In a similar way to anti-HIV drugs, however, NUCs seldom eradicate the virus, forcing people with HBV to have lifelong treatment to prevent dangerous recurrences of liver disease.
A prevailing dogma in the HBV field has been borrowed from studies of other chronic infections. It asserts that reducing viral antigens in the blood or liver especially the hepatitis B surface antigen, or HBsAg might awaken immune cells called T cells so that they will fight the virus and clear the chronic infection. Accordingly, several therapeutic approaches that either reduce levels of viral antigens in the circulation or decrease their production in the liver have already reached the clinic, both alone and in combination with NUCs or interferon.
Part of Nature Outlook: Hepatitis B
More from Nature Outlooks
Disclosing Your Child’s Diagnosis
If you decide to disclose your child’s hepatitis B, remain calm, provide literature to reinforce the facts, and give the school a letter from your child’s doctor stating that s/he is healthy and poses no risk to the other children if appropriate precautions are maintained. Most states require hepatitis B vaccination prior to school entry, so this reduces any potential risk to other students.
We recommend the following when disclosing your child’s hepatitis B to school officials:
- Stress the importance of confidentiality and universal precautions to protect your child from social discrimination.
- Remind school officials that hepatitis B is transmitted through exposure to blood it is not transmitted casually.
- Explain that hepatitis B is not the only blood-borne disease that puts children at risk.
- Consider saying “Treat my child as you should treat every child – with care. You know what risk my child poses, but you don’t know the risk that other children might present.”
Don’t Miss: How Many Kinds Of Hepatitis Are There
What Other Problems Can Hepatitis B Cause
In rare cases, acute hepatitis B can cause liver failure.
If you have ever had hepatitis B, the virus may become active again, or reactivated, later in life. This could start to damage the liver and cause symptoms.
Donât Miss: What Can Cause Hepatitis C
Nucleoside Analogues Or Oral Antivirals
Antivirals, or NAs, slow down or stop the hepatitis B virus from reproducing, decreasing the risk of liver damage. Less liver damage occurs when there is less virus present.
People take NAs orally as a pill and experience very few side effects.
First-line treatments, such as Tenofovir disoproxil and entecavir, are potent and effective in suppressing the virus, but they only work for as long as a person takes them. Discontinuing treatment
Also Check: Is A Vaccine Available For Hepatitis B
Injections: Interferon And Pegylated Interferon
Pegylated interferon is given as an injection once per week. It can be used alone or with an oral hepatitis B medication. Patients with both chronic hepatitis B and hepatitis D infection may need pegylated interferon alone or combined with an oral hepatitis B pill.
- Pegylated interferon therapy is usually given for 48 weeks.
- Pegylated interferon may cause many side effects, such as flu-like symptoms, rashes, irritability, and depression.
- Side effects to interferon require close monitoring with routine blood tests.
Whats The Difference Between Acute And Chronic Hepatitis B
Hepatitis B can be either acute or chronic:
- Acute hepatitis B lasts for a short period of time. If you have acute hepatitis B, you may be asymptomatic or have symptoms and develop icteric hepatitis. It can transition into chronic hepatitis B if the virus doesnt naturally go away after 6 months.
- Chronic hepatitis B lasts for at least 6 months. If you have this type of hepatitis, you may carry the hepatitis B virus for the rest of your life. Its possible to have chronic hepatitis B that started as acute, but many people dont have acute hepatitis B first.
Most people with acute hepatitis B make a full recovery. Some may never even show any symptoms. But those with chronic hepatitis B often need treatment to help manage the infection. Chronic hepatitis B also increases your risk of developing cirrhosis and certain types of liver cancer.
Your risk of developing chronic hepatitis B depends on when you first received your diagnosis of the virus. Children who receive a diagnosis of hepatitis B, especially those under the age of 5 years old, have a higher risk of the infection becoming chronic. Adults are less likely to develop chronic hepatitis B. Around 90 percent of adults who develop it will fully recover.
Keep in mind that hepatitis B can be present for years before you start to show any symptoms.
Also Check: Frequency Of Hepatitis B Vaccine
Clinical Relevance And Detection Of Drug Resistance
The clinical relevance of drug resistance became dramatically clear after the introduction of the first nucleoside analogue LMV that has a low barrier to resistance. LMV-resistant mutations arise in about 23% of patients after 12 months of therapy and in up to 80% after 5 years of treatment . Patients with LMV-resistant mutations have a higher risk of deteriorating liver function , increasing signs of liver injury as well as developing cirrhosis and hepatocellular carcinoma, all in comparison to patients with wildtype virus under antiviral therapy . Viral rebound and hepatic decompensation is also observed with other drug-resistant HBV mutants . The risk of selecting antiviral therapy-resistant mutants is related to the pretreatment HBV DNA level, the choice of the antiviral , the duration of treatment, the rapidity of viral response/viral suppression as well as to the previous exposure to nucleotide/nucleoside analogues . In order to reduce the risk of drug resistance, all guidelines now recommend the use of newer, highly potent antivirals with a high barrier to resistance such as ETV or TDF .
Choice Of Antiviral Drug And Duration Of Treatment
For patients who are eligible to receive either IFN or NA therapy, the choice depends on patient preference and predicted likelihood of response. IFN has to be administered as injections and is associated with many side effects, but it is given for a finite duration and has a higher rate of HBeAg and HBsAg loss, particularly for patients with genotype A infection. Patients who are HBeAg-positive with genotype A infection, high ALT , and low HBV DNA with no cirrhosis and no contraindications to the use of IFN are the best candidates for IFN therapy.
NAs are taken orally and have negligible side effects but need to be administered for many years and in some patients for life. Thus, willingness to commit to a long duration of treatment and ability to adhere to the treatment are important deciding factors. ETV, TDF, and TAF are preferred NAs. ETV or TAF is preferred for patients with underlying renal or bone disease. TDF or TAF should be used in patients with prior NA exposure. TDF should be used in pregnant women and women contemplating pregnancy.
Don’t Miss: Can Hepatitis B Be Cured With Antibiotics