Asked By: Gilbert Gonzalez Date: created: Jan 06 2023

What is the HBV cure 2023

Answered By: Adam Morris Date: created: Jan 08 2023

The Science of HBV Cure Meeting 2023 Scientific Programme – HBV Cure 2023 is designed for Scientists (virologists, Immunologists), Clinician Scientists, pharmacists and Industry Experts, to exchange information on the latest research, discuss new developments in the cure for Hepatitis B Virus – a disease which still plagues hundreds of millions of people. We invite all interested parties to present their research papers. Click on bellow Abstracts and Posters for further information. Abstracts will be reviewed by the Abstract Selection Committee and accepted submissions will be posted on Abstract & Poster Gallery in our website and in the Poster Hall. Some travel grants will be available to selected Presenters.

Has anyone been cured of hepatitis B?

Great progress has been made in treating the virus, though more can be done – There is currently no cure for people living with chronic hepatitis B virus infection. Those unable to naturally fight off the virus may live with it for many years without experiencing any symptoms until the liver becomes damaged.

  1. Because of this, people diagnosed with chronic hepatitis B virus infection need to be regularly tested and monitored to watch out for liver damage.
  2. Additionally, we recognise that people living with chronic hepatitis B virus infection may also endure significant psychological pain and social stigma.
  3. Although most transmission occurs from mother to child during birth, there are other routes of transmission which can cause people to view their condition as something shameful, potentially reducing their likelihood to seek care and their quality of life.

Current hepatitis B treatments work to suppress the activity of the virus, keeping it inactive with antiviral therapies. These treatments can help protect the liver but rarely clear the virus completely. This means many people with hepatitis B require treatment for the rest of their lives.

To get ahead of hepatitis B, scientists are looking at innovative ways to address both the viral infection and the resulting immune dysfunction which allows the virus to persist in the body long term. With hepatitis B virus infection, the virus both embeds its DNA into our liver cells and hijacks the cell’s own processes to produce proteins for the virus.

Current treatments seek to minimise the effects of the virus by focusing on the viral DNA replication process. Scientists are now looking to go one step further by switching the focus to the virus’ RNA. They have discovered that interfering with the RNA not only stops viral replication but also halts the production of viral proteins and allows for an opportunity to investigate whether this can stop hepatitis B in its tracks.

Who moves to end hepatitis by 2030?

Hepatitis is an inflammation of the liver that is caused by a variety of infectious viruses and noninfectious agents leading to a range of health problems, some of which can be fatal. There are five main strains of the hepatitis virus, referred to as types A, B, C, D and E.

  • While they all cause liver disease, they differ in important ways including modes of transmission, severity of the illness, geographical distribution and prevention methods.
  • In particular, types B and C lead to chronic disease in hundreds of millions of people and together are the most common cause of liver cirrhosis, liver cancer and viral hepatitis-related deaths.

An estimated 354 million people worldwide live with hepatitis B or C, and for most, testing and treatment remain beyond reach. Some types of hepatitis are preventable through vaccination. A WHO study found that an estimated 4.5 million premature deaths could be prevented in low- and middle-income countries by 2030 through vaccination, diagnostic tests, medicines and education campaigns.

  1. WHO’s global hepatitis strategy, endorsed by all WHO Member States, aims to reduce new hepatitis infections by 90% and deaths by 65% between 2016 and 2030.
  2. Many people with hepatitis A, B, C, D or E exhibit only mild symptoms or no symptoms at all.
  3. Each form of the virus, however, can cause more severe symptoms.

Symptoms of hepatitis A, B and C may include fever, malaise, loss of appetite, diarrhoea, nausea, abdominal discomfort, dark-coloured urine and jaundice (a yellowing of the skin and whites of the eyes). In some cases, the virus can also cause a chronic liver infection that can later develop into cirrhosis (a scarring of the liver) or liver cancer.

  • These patients are at risk of death.
  • Hepatitis D (HDV) is only found in people already infected with hepatitis B (HBV); however, the dual infection of HBV and HDV can cause a more serious infection and poorer health outcomes, including accelerated progression to cirrhosis.
  • Development of chronic hepatitis D is rare.

Hepatitis E (HEV) begins with mild fever, reduced appetite, nausea and vomiting lasting for a few days. Some persons may also have abdominal pain, itching (without skin lesions), skin rash or joint pain. They may also exhibit jaundice, with dark urine and pale stools, and a slightly enlarged, tender liver (hepatomegaly), or occasionally acute liver failure.

Safe and effective vaccines are available to prevent hepatitis B virus (HBV). This vaccine also prevents the development of hepatitis D virus (HDV) and given at birth strongly reduces transmission risk from mother to child. Chronic hepatitis B infection can be treated with antiviral agents. Treatment can slow the progression of cirrhosis, reduce incidence of liver cancer and improve long term survival.

Only a proportion of people with chronic hepatitis B infection will require treatment. A vaccine also exists to prevent infections of hepatitis E (HEV), although it is not currently widely available. There are no specific treatments for HBV and HEV and hospitalization is not usually required.

It is advised to avoid unnecessary medications due to the negative effect on liver function caused by these infections. Hepatitis C (HCV) can cause both acute and chronic infection. Some people recover on their own, while others develop a life-threatening infection or further complications, including cirrhosis or cancer.

There is no vaccine for hepatitis C. Antiviral medicines can cure more than 95% of persons with hepatitis C infection, thereby reducing the risk of death from cirrhosis and liver cancer, but access to diagnosis and treatment remains low. Hepatitis A virus (HAV) is most common is low- and middle-income countries due to reduced access to clean and reliable water sources and the increased risk of contaminated food.

Can I live long with hepatitis B?

If you test positive for the hepatitis B virus for longer than 6 months, this indicates that you have a chronic hepatitis B infection. All patients with chronic hepatitis B infections, including children and adults, should be monitored regularly since they are at increased risk for developing cirrhosis, liver failure, or liver cancer.

You should make an appointment with a hepatologist (liver specialist) or gastroenterologist familiar with hepatitis B. This specialist will order blood tests and possibly a liver ultrasound to evaluate your hepatitis B status and the health of your liver. Your doctor will probably want to see you at least once or twice a year to monitor your hepatitis B and determine if you would benefit from treatment.

Not everyone who tests positive for hepatitis B will require medication. Depending on your test results, you and your doctor might decide to wait and monitor your condition. If your test results indicate that you would be a good candidate for treatment, then your doctor will discuss the current treatment options with you.

Whether you start treatment or not, your doctor will want to see you every six months, or at minimum once every year. Before you start any treatment, make sure you research each treatment option, and ask your doctor to thoroughly explain each option, so that you are well informed. It also might be a good idea to get a second opinion from another doctor before starting any treatment, because more information is always better! Once you are diagnosed with chronic hepatitis B, the virus will most likely stay in your blood and liver for a lifetime.

It is important to know that you can pass the virus along to others, even if you don’t feel sick. This is why it’s so important that you make sure that all close household contacts and sex partners are tested and vaccinated against hepatitis B. While living with hepatitis B can be difficult and scary at first, the more information and support that you have, the easier it gets.

Many patients become such experts at managing their hepatitis B that they sometimes teach their health care providers about the latest research and information! The most important thing to remember is that hepatitis B is a chronic medical condition (such as diabetes and high blood pressure) that can be successfully managed if you take good care of your health and your liver.

You should expect to live a long, full life.

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Is hepatitis B good for life?

Hepatitis B VIS (Interim) Hepatitis B Vaccine: What You Need to Know Current Edition Date: 5/12/2023 Hepatitis B vaccine can prevent hepatitis B, Hepatitis B is a liver disease that can cause mild illness lasting a few weeks, or it can lead to a serious, lifelong illness.

Acute hepatitis B is a short-term illness that can lead to fever, fatigue, loss of appetite, nausea, vomiting, jaundice (yellow skin or eyes, dark urine, clay-colored bowel movements), and pain in the muscles, joints, and stomach. Chronic hepatitis B is a long-term illness that occurs when the hepatitis B virus remains in a person’s body. Most people who go on to develop chronic hepatitis B do not have symptoms, but it is still very serious and can lead to liver damage (cirrhosis), liver cancer, and death. Chronically infected people can spread hepatitis B virus to others, even if they do not feel or look sick themselves.

Hepatitis B is spread when blood, semen, or other body fluid infected with the hepatitis B virus enters the body of a person who is not infected. People can become infected through:

Birth (if a pregnant person has hepatitis B, their baby can become infected) Sharing items such as razors or toothbrushes with an infected person Contact with the blood or open sores of an infected person Sex with an infected partner Sharing needles, syringes, or other drug-injection equipment Exposure to blood from needlesticks or other sharp instruments

Most people who are vaccinated with hepatitis B vaccine are immune for life. Hepatitis B vaccine is usually given as 2, 3, or 4 shots. Infants should get their first dose of hepatitis B vaccine at birth and will usually complete the series at 6–18 months of age.

  1. The birth dose of hepatitis B vaccine is an important part of preventing long-term illness in infants and the spread of hepatitis B in the United States.
  2. Anyone 59 years of age or younger who has not yet gotten the vaccine should be vaccinated.
  3. Hepatitis B vaccination is recommended for adults 60 years or older at increased risk of exposure to hepatitis B who were not vaccinated previously.

Adults 60 years or older who are not at increased risk and were not vaccinated in the past may also be vaccinated. Hepatitis B vaccine may be given as a stand-alone vaccine, or as part of a combination vaccine (a type of vaccine that combines more than one vaccine together into one shot).

Has had an allergic reaction after a previous dose of hepatitis B vaccine, or has any severe, life-threatening allergies

In some cases, your health care provider may decide to postpone hepatitis B vaccination until a future visit. Pregnant or breastfeeding people who were not vaccinated previously should be vaccinated. Pregnancy or breastfeeding are not reasons to avoid hepatitis B vaccination.

Soreness where the shot is given, fever, headache, and fatigue (feeling tired) can happen after hepatitis B vaccination.

People sometimes faint after medical procedures, including vaccination. Tell your provider if you feel dizzy or have vision changes or ringing in the ears. As with any medicine, there is a very remote chance of a vaccine causing a severe allergic reaction, other serious injury, or death.

An allergic reaction could occur after the vaccinated person leaves the clinic. If you see signs of a severe allergic reaction (hives, swelling of the face and throat, difficulty breathing, a fast heartbeat, dizziness, or weakness), call 9-1-1 and get the person to the nearest hospital. For other signs that concern you, call your health care provider.

Adverse reactions should be reported to the Vaccine Adverse Event Reporting System (VAERS). Your health care provider will usually file this report, or you can do it yourself. Visit the or call 1-800-822-7967, VAERS is only for reporting reactions, and VAERS staff members do not give medical advice.

  • The National Vaccine Injury Compensation Program (VICP) is a federal program that was created to compensate people who may have been injured by certain vaccines.
  • Claims regarding alleged injury or death due to vaccination have a time limit for filing, which may be as short as two years.
  • Visit the or call 1-800-338-2382 to learn about the program and about filing a claim.

Vaccine Information Statement (Interim) Hepatitis B Vaccine (5/12/2023) 42 U.S.C. § 300aa-26 Department of Health and Human Services Centers for Disease Control and Prevention Office Use Only : Hepatitis B VIS (Interim)

How many recover from hepatitis B?

Up to 50% of infected children (1-5 years) will develop a chronic hepatitis B infection.5-10% of infected adults will develop a chronic hepatitis B infection (that is, 90% will recover)

Is hepatitis B declining?

How Many People Have Hepatitis B? – In the United States, an estimated 880,000 to 1.89 million people are chronically infected with HBV. New cases of HBV infection in the United States had been decreasing until 2012. Since that time, reported cases of acute hepatitis B have been fluctuating around 3,000 cases per year.

  1. In 2020, 2,157 cases of acute hepatitis B were reported; however, because of low case detection and reporting, the Centers for Disease Control and Prevention (CDC) estimates that there were 14,000 acute hepatitis B infections.
  2. The rate of acute cases of HBV decreased by 32% after 2019 which may be related to the disruptions of the COVID-19 pandemic.

For the most recent surveillance data visit CDC Viral Hepatitis Surveillance, Globally, HBV is the most common blood-borne infection with an estimated 296 million people infected according to the World Health Organization,

Asked By: Christopher Harris Date: created: Jul 13 2023

Is there a cure for hepatitis B in 2028

Answered By: Herbert Long Date: created: Jul 14 2023

New treatment for Hepatitis B with vaccine New trials published with hepatitis B patients suggests the use of liposome nanoparticles with virus antigens for their treatment. It is estimated that in the world, about 240 million people have and that 4.7 million new cases are diagnosed annually.

  • Since chronic hepatitis B is responsible for 30% of liver cirrhosis and 53% of liver cancer, the has set a goal of eliminating chronic hepatitis B by 2030.
  • In this sense, there is a very useful vaccine to prevent hepatitis B virus infection but, although there are effective antiviral drugs to prevent liver damage caused by hepatitis B virus, there are no treatments capable of eliminating the virus.

In an infected person, a correct immune response is essential to eliminate the hepatitis B virus, and so, different therapeutic vaccines are being developed. A clinical trial assessing liposome nanoparticles (lipid spheres) that carry hepatitis B virus antigens within them and that are capable of significantly increase defenses against the virus, has been published in the,

The study included 354 patients with chronic hepatitis B, 235 of them receiving 6 subcutaneous injections of therapeutic liposomal nanoparticles at 0, 4, 8, 12, 20 and 28 weeks, while the other 119 patients were injected with placebo (empty nanoparticles). It was found that 18% of the patients responded to the therapeutic vaccine treatment compared to 5% of those who received the placebo.

In Europe, a clinical trial will begin in 2022 to evaluate the efficacy of another therapeutic vaccine against hepatitis B virus, TherVacB, If the results are satisfactory, its use is expected to be approved by 2028. In summary, it seems clear that the way to cure hepatitis B is the use of therapeutic vaccines, although new studies are still needed to determine the type of vaccine, dose and duration of treatment to obtain maximum efficacy.

Which hepatitis is life long?

How serious is chronic (long-term) hepatitis B? – Chronic hepatitis B can develop into a serious disease resulting in long-term health problems, including liver damage, liver failure, liver cancer, and even death. There were 1,752 deaths related to hepatitis B virus reported to CDC in 2020, but this is an underestimate.

Asked By: Richard Murphy Date: created: Feb 19 2024

Which hepatitis is lifelong

Answered By: Jake Lopez Date: created: Feb 21 2024

Key facts –

Hepatitis A is an inflammation of the liver that can cause mild to severe illness. The hepatitis A virus (HAV) is transmitted through ingestion of contaminated food and water or through direct contact with an infectious person. Almost everyone recovers fully from hepatitis A with a lifelong immunity. However, a very small proportion of people infected with hepatitis A could die from fulminant hepatitis. The risk of hepatitis A infection is associated with a lack of safe water and poor sanitation and hygiene (such as contaminated and dirty hands). A safe and effective vaccine is available to prevent hepatitis A.

Asked By: Fred King Date: created: Dec 19 2023

Can I still get hepatitis B even if I was vaccinated

Answered By: Logan Cooper Date: created: Dec 20 2023

Courtesy of Google Images A hepatitis B diagnosis can be scary and confusing for both you and your loved ones, especially if you are unfamiliar with the virus. Hepatitis B is known to be sexually transmitted, and you may wonder how you can continue your relationship with someone who has been infected.

The good news is that hepatitis B is vaccine preventable. This means that after you complete the vaccine series, you cannot contract hepatitis B through any modes of transmission; you are protected for life! However, it is important to remember that the vaccine will only work if a person has not been previously infected.

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Therefore, it is necessary to take certain steps after your partner’s diagnosis to protect yourself from becoming infected. The first step is to visit the doctor and get tested, even if you think that you do not have it. Since hepatitis B often has no symptoms for decades, testing is the only way to know your status.

  1. The doctor should perform the Hepatitis B Panel test – a simple blood draw that shows hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb or anti-HBs), and hepatitis B core antibody total (HBcAb or anti-HBc).
  2. Looking at these three blood test results together will show if you have a current infection, have recovered from a past infection, or if you need to be protected through vaccination.

Once you receive your results, this chart can help you understand what they mean. Preventing Transmission through Vaccines: If you test negative for HBsAg, HBsAb, and HBcAb, you are not protected from hepatitis B and are considered to have a high risk of contracting the virus from your partner or other means. The hepatitis B vaccine is a 3-shot series taken over the span of 6 months. The first shot can be given at any time. The second dose should be given at least one month after the first shot, and the third and final dose should be separated from dose 2 by at least two months and dose 1 by at least 4 months.

While there is a minimum amount of time required between doses, there is no maximum amount of time. If you miss your second or third shot, you do not have to start the series over again; you can pick up where you left off! If your partner is pregnant and was diagnosed with hepatitis B, extra precautions need to be taken to prevent transmission to the child.

Two shots will need to be given to the child in the delivery room: the first dose of the hepatitis B vaccine and Hepatitis B Immune Globulin (HBIG), if recommended and available in your country. You can learn more about pregnancy and hepatitis B here,

  • After completing the series, a quick blood test called the “antibody titer” (anti-HBs titer) test can confirm that you have responded to the vaccine.
  • This test, which should be given at least one month after you receive the third dose, will be greater than 10 mIU/mL if you are protected from hepatitis B.

Like the vaccine, your doctor can administer the titer test. Hepatitis B is spread through direct contact with blood. HBV is also a sexually transmitted disease, so it is important to practice safe sex by using condoms throughout the duration of the vaccine series until the antibody titer test confirms that you are protected.

  • While you wait for your body to create its defense, there are other steps that you can take to avoid transmission such as not sharing toothbrushes or sharp objects like razors.
  • The hepatitis B vaccine is the only way to fully protect yourself from the virus.
  • Preventive measures such as using condoms can help prevent hepatitis B transmission, but without vaccination, there can still be some risk.

If you do not have a doctor or are worried about the cost of testing or vaccination, you can still get tested and vaccinated! In the United States, Federally Qualified Health Centers provide the hepatitis B vaccine at low- or no cost to individuals without insurance or with limited plans.

What is the 5 year survival rate of hepatitis B?

Survival Rates The 5-year survival rate from liver cancer varies from about 10% to 14%. This survival rate is low partly because many people with liver cancer also have cirrhosis, which itself is a serious liver disease. Cirrhosis and liver cancer together is a very dangerous combination.

The good news is that survival rates are greatly improved with regular screening for those at high risk (such as people chronically infected with hepatitis B or C), because early detection results in more treatment options.The 5-year survival rates can be over 50% for people with small, resectable tumors that are removed and who do not have cirrhosis or other serious health problems.For people with early-stage liver cancer who are able to have a liver transplant, the 5-year survival rate ranges from 60% to 70%.

Why is there no cure for HBV?

How is it currently treated? – There is no cure for chronic hepatitis B virus. In most cases, treatment requires taking a pill every day for life to remain effective and to reduce the risk of liver cancer. Even then, it doesn’t eliminate the risk. Chronic hepatitis B hasn’t been cured so far in part because current therapies have failed to destroy the viral reservoir, where the virus hides in the cell.

  1. This is in contrast to hepatitis C virus, which has no such viral reservoir and can now be cured with as little as 12 weeks of treatment.
  2. Read more: In contrast to Australia’s success with hepatitis C, our response to hepatitis B is lagging Despite the huge human and economic toll of chronic hepatitis B, research to cure the disease remains underfunded.

There is a misconception that because there is a vaccine, hepatitis B is no longer a problem. The availability of effective cures for the unrelated hepatitis C virus has also led people to believe that “viral hepatitis” is no longer a problem. Experts estimate that liver cancer deaths will substantially increase in coming decades without a cure for hepatitis B, despite deaths from most cancers decreasing. Hepatitis B causes 40% of all liver cancer. Napocska/Shutterstock

Asked By: Blake Brown Date: created: Mar 01 2023

What is the cure rate of HBV

Answered By: Douglas Ward Date: created: Mar 03 2023

Emerging Therapies Toward a Functional Cure for Hepatitis B Virus Infection G&H Currently, what is the burden of hepatitis B virus infection in the United States? RK Population surveys have suggested that there are between 700,000 and 800,000 people living with hepatitis B virus (HBV) infection in the United States.

  1. However, those population surveys tend to miss people with a high prevalence of HBV infection, including recent immigrants and institutionalized people.
  2. Altogether, it has been suggested that up to 1.5 to 2 million people in the United States may actually have HBV infection.
  3. Ideally, the treatment goal would be to cure HBV infection.

G&H What should be the goal of HBV treatment? RK The current goal is limited by the tools that are available to treat the disease. These tools, namely oral HBV polymerase inhibitors, are very effective at suppressing the virus from replicating and preventing damages to the liver, but they are not curative (unlike hepatitis C virus treatment).

  • Thus, the current treatment goal is remission of liver disease by effective suppression of HBV.
  • It is important to keep in mind that this treatment goal can only be achieved in patients who are diagnosed with HBV infection and are being followed, and that there are many people living with HBV infection who have not even been diagnosed or connected to the health care system.

Therefore, a larger health care system–wide goal is to provide treatment to all people at risk of future complications so that they can be prevented. It should also be pointed out that, ideally, the treatment goal would be to cure HBV infection. Although achieving that goal is not currently possible, there are many compounds being tested at the present time.

Hopefully in the next decade, there will be a cure for this disease. G&H How can functional cure of HBV infection be defined? RK The prevailing definition of functional cure at the present time is loss of hepatitis B surface antigen (HBsAg) in the blood. However, what this means biologically is not completely understood.

There are several barriers to cure, one of which involves covalently closed circular DNA, a sort of viral chromosome in the liver cells of an infected person. This replication template is not affected by the current polymerase inhibitors. Another barrier is that some of the viral genome is inserted into host chromosomes, which can generate viral proteins.

  1. The extent to which this contributes to the maintenance of chronic infection is unknown, as is whether it is possible to achieve functional cure by interrupting the viral cycle at different points.
  2. Functional cure may not translate to complete cure because of the viral genome fragments that persist in the host cells.

Partial List of HBV Direct-Acting Antiviral Candidate Compounds in Human Trials

Drug Company Latest Trial Phase
siRNAs
ARB-1467 Arbutus Biopharma Phase 2
ARB-1740 Arbutus Biopharma Phase 2
RG6004 (HBV LNA) Roche Phase 1/2
ARO-HBV Arrowhead Phase 1/2
Entry Inhibitor
Myrcludex B Hepatera/MYR Phase 2
Capsid Inhibitors
NVR 3-778 Janssen Phase 2
JNJ-56136379 Janssen Phase 1
ABI-H0731 Assembly Biosciences Phase 1
AB-423 Arbutus Biopharma Phase 1
HBsAg Inhibitors
REP 2139 Replicor Phase 2
REP 2165 Replicor Phase 2

G&H What treatment approaches or targets are currently being used for HBV infection, and what are their functional cure rates to date? RK Currently, only 2 classes of HBV treatment agents are available. One is interferon, which is an immunomodulatory drug as well as an antiviral agent. Interferon has a low functional cure rate, but the rate varies according to the host phase of infection. People who are younger and have more active underlying liver inflammation tend to respond better, whereas older people with less inflammatory activity have a lower cure rate. After interferon therapy, the functional cure rate is, at most, 20%. In functional cure with interferon, a certain percentage of HBsAg loss can occur after treatment is completed. The other class of medicine for current HBV treatment consists of HBV polymerase inhibitors, often called nucleoside or nucleotide analogues. These agents are very effective at suppressing the virus by blocking the viral enzyme needed for the virus to replicate itself. However, they do nothing directly to the host immune system, and their functional cure rate is lower than that of interferon (<10% over many years of follow-up). G&H What treatment approaches or targets are currently being investigated for HBV infection? RK There are many classes of targets currently under investigation, some of which are listed in the Table. One class blocks the entry of HBV into hepatocytes, as the virus usually takes advantage of a receptor to insert itself into the cytoplasm of a hepatocyte. One agent in this class (Myrcludex B, Hepatera/MYR) is being tested in a phase 2 clinical trial. Another class undergoing fairly active investigation involves small interfering RNAs. This class targets the viral genome in different areas to disrupt viral protein production and interrupt its life cycle. Within this class, there are several compounds being tested, and the difference between them relates to the region of the RNA that each is targeting and how the RNAs are introduced into hepatocytes. Capsid inhibitors comprise another class of agents currently undergoing investigation for HBV treatment. Capsid, the protein surrounding the viral genome, plays multiple roles, allowing capsid inhibitors to have multiple modes of inhibiting HBV. Currently, several of these agents are being tested. Another class in clinical development consists of HBsAg inhibitors. The last step of the HBV life cycle is for the virus (or surface protein) to be exocytosed, and this particular class of chemical inhibits HBsAg from being processed and released outside of the cell. Interestingly, this seems to trigger an immune reaction from the host, as the viral proteins circulating in the body may play a role in paralyzing the immune response. Preliminary studies indicate that, when combined with other antiviral agents, a HBsAg inhibitor may help patients restore their immune function, leading to HBsAg loss and sometimes hepatitis B surface antibody production. In addition, there are a number of agents purported to improve host immune response against HBV. Some of them are innate immune enhancers, including Toll-like receptor agonists. Also in early development is a RIG-I activator that triggers interferon response, as well as directly interrupts HBV replication. Finally, there are a number of agents targeting the adaptive immune system. For example, programmed cell death protein 1 and programmed death-ligand 1 inhibitors are checkpoint inhibitors that have led some patients to lose HBsAg by breaking the immune tolerance that perpetuates the infection. A number of therapeutic vaccines are under development as well. Once HBV is incorporated into the host genes, it is a challenge to remove it. G&H What clinical trial data are available on these agents? RK The clinical trial data are either phase 1 or 2 at most, so they are not very mature, but they are promising. However, there have not yet been large-enough trials to conclusively tell us that any of these molecules will consistently provide high rates of functional cure that are clinically meaningful. G&H Overall, what appears to be critical for achieving functional cure? RK The data to date seem to indicate that 2 components are needed. One is to fundamentally disrupt the viral life cycle, and the other is to encourage the host immune system to try to break through the tolerance that is preventing cure of the infection. My interpretation of the emerging data is that both of these components have to work together. Therefore, some element of immunomodulators is likely necessary, at least in the beginning stages of the cure effort, as well as direct-acting antiviral agents with viral or intracellular targets. Identifying what may be the ideal combination seems to be what most researchers are trying to figure out because none of the compounds previously mentioned appear to completely eliminate the virus by themselves. The data are promising for curing the virus, as compared to merely suppressing it, but we are not there yet. We would like to be able to achieve what we have come to expect with HCV. A major unknown factor in functional cure of HBV is the integration of HBV DNA into the host. Once HBV is incorporated into the host genes, it is a challenge to remove it. This is thought to be an important barrier to achieving functional cure, but it remains to be seen whether this will continue to be the case as better treatments are developed. Another issue is at what cost we should try to achieve functional cure. Currently, there are very effective viral suppressive medicines that drive the hepatitis B viral load to zero (ie, undetectable levels) as well as cause the patient's liver inflammation to disappear and the progression of liver disease to halt (and sometimes even reverse). Those agents achieve very good outcomes without too many long-term safety concerns, so the bar is set fairly high that (1) functional cure should actually provide more advantage to the patient and (2) functional cure could be achieved safely. It is unknown what it means to have HBsAg disappear if all that it accomplishes is status quo plus cosmetic disappearance of the antigen. Does that simply mean patients would be able to stop taking suppressive medicine long term? Or does functional cure really mean fundamental alteration of the natural history of the infection (ie, eliminating the risk of liver cancer, which would be groundbreaking)? This issue remains to be sorted out. G&H Are there any data showing that the elimination of HBsAg is actually meaningful? RK Proponents of functional cure as the next endpoint point to data obtained from people who experience HBsAg loss, untreated or treated with the currently available medications. They observe that patients who lose HBsAg have much better outcomes over time than patients who fail to lose HBsAg. However, these 2 groups of people are often too different to compare. People who lose HBsAg on their own, or even those who are taking the currently available antiviral agents (particularly nucleoside/nucleotide analogues), may have something in their body, perhaps in their immune system, that lets them achieve functional cure. Their underlying ability (ie, a host factor) may be what is driving the apparent benefit of HBsAg loss rather than the fact that the HBsAg has become undetectable in their blood. G&H Is it possible that a single drug may be able to achieve functional cure of HBV? RK Thus far, the data seem to suggest that none of the compounds being tested may be sufficient individually to achieve functional cure. At the present time, I think it is likely that some type of combination will be needed, perhaps one that works on intracellular targets and another on host immune cells. G&H Is achieving functional cure a feasible goal for all HBV patients in the near future? RK It depends on how the near future is defined. I have been telling my patients that a functional cure may come within 5 years for the past 5 years, so I have stopped trying to predict the future. However, I suspect that patients whose disease activity is controlled on their own or by long-term antiviral medications will likely be the easiest to lead to functional cure. Nevertheless, it is important to keep in mind that HBV is a difficult disease to cure. People may have unrealistic expectations due to the recent success of HCV drugs for completely eliminating the disease in the vast majority of patients. However, these 2 diseases are quite different. Even if functional cure of HBV is achieved, the viral genetic material is likely to remain in the host; therefore, the extent of risk reduction associated with functional cure is likely to be smaller. The biggest concern for HBV patients is liver cancer. There is a real risk of liver cancer, even when the virus is suppressed. G&H What are the most important next steps in research in this area? RK One of the most important next steps is to determine what combination of drugs may be most effective for HBV treatment. As previously discussed, there are many compounds being developed, but a combination will likely be needed. Then, I think the next challenge will be to take the tools that are developed and apply them to people living with HBV infection throughout the world. The latest statistics from the World Health Organization state that 250 to 300 million people in the world are infected with HBV, making this disease a significant public health problem worldwide. : Emerging Therapies Toward a Functional Cure for Hepatitis B Virus Infection