Hepatitis B Functional Cure

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Hepatitis B Functional Cure
Functional cure is defined as loss of hepatitis B surface antigen (HBsAg) and undetectable hepatitis B virus (HBV) DNA after 6 months off therapy ; it is associated with improved clinical outcomes and is the optimal goal of therapy for chronic hepatitis B.

What is the functional cure for hepatitis B and immune response?

Introduction – The infection of chronic hepatitis B virus (HBV) is still a worldwide problem that seriously threatens human health. It is the principal reason of end-stage liver diseases, including cirrhosis and hepatocellular carcinoma (HCC). As WHO estimated, there were 290 million people infected with chronic HBV all over the world in 2019, and about 1.5 million people were newly infected each year ( 1 ).

The prevalence rate of HBsAg among the general people in China is 6.1%, and there are about 86 million people with positive HBsAg ( 2 ). More than 90% of HCC in China is related to chronic HBV infection. At present, there are two kinds of widely used anti-HBV drugs, namely nucleos(t)ide analogues (NAs) as well as peginterferon-α (PegIFNα).

The treatment goal determined by domestic and foreign guidelines is to improve the long-term outcomes by maximizing the persistent inhibition of HBV ( 3 – 5 ). The goal of CHB treatment is to pursue cure. According to HBV related biomarkers and possible outcomes, hepatitis B cure can be divided into partial cure, functional cure (clinical cure) and complete cure ( 6 ).

  1. Because of covalently closed circularDNA (cccDNA) existence and integrated HBV DNA in hepatocytes, HBV cannot be completely eliminated, but functional cure, that is, the clearance of HBsAg, becomes possible.
  2. The so-called functional cure refers to achieving HBsAg seroclearance, with or without positive anti-HBs, based on continuous undetectable HBV DNA and HBeAg after a finite course of treatment.

It can be originated from the induction of PegIFN based regimens or NAs, and the spontaneous clearance of HBsAg ( 7 ). Chronic hepatitis B (CHB) is an immune related disease. HBV does not directly damage the liver but through abnormal immune response. The interaction between the replication of virus and the antiviral immunity of host determines the final result of HBV infection.

  1. The responses of host’s innate and specific immunity to the virus promote the clearance of HBV in patients with acute hepatitis B.
  2. HBV continues to replicate and the host immune response is insufficient in patients with CHB.
  3. Integration of HBV DNA in hepatocytes, persistent presence of HBV cccDNA, dysfunction of T cells and insufficient response of B cells are the major obstacles to eliminate HBV.

This determines that CHB cannot be completely cured through direct antiviral agents as chronic hepatitis C. Therefore, in order to cure hepatitis B, it is more important to restore host immune function in addition to inhibiting virus replication, reducing or even eliminating virus antigens ( 8 ).

Can your body fight off chronic hepatitis B?

What is Hepatitis B? – Hepatitis B is a contagious liver infection caused by the hepatitis B virus (HBV). The natural course of hepatitis B disease is different from one person to another.

The first phase of disease, during the first 6 months after a person becomes infected, is called acute hepatitis B infection. During this phase, many people show no symptoms at all. Among those who do have symptoms, the illness is usually mild and most people don’t recognize that they have liver disease. In 90% of persons who become infected as adults with hepatitis B, the immune system successfully fights off the infection during the acute phase — the virus is cleared from the body within 6 months, the liver heals completely, and the person becomes immune to hepatitis B infection for the rest of their life. In the other 10%, the immune system cannot clear the virus and hepatitis B infection persists past 6 months, usually for the rest of the person’s life. This persistent state is known as chronic hepatitis B infection. When babies become infected at birth or during infancy, the percentages are reversed — only 10% clear the infection. The remaining 90% develop chronic hepatitis B infection. In chronic hepatitis B infection, the liver becomes inflamed and scarred over a period of years. However, the speed at which inflammation and scarring take place varies between people. Some develop severe liver scarring (cirrhosis) within 20 years. In others, liver disease progresses slowly and does not become a major problem during their lifetime. Another concern is the potential for liver cancer. Hepatitis B infection is the single most important cause of hepatocellular (liver) cancer.

Treatment with anti-viral drugs works for some people with HBV who are starting to develop liver damage. Whether treatment will be successful depends on many factors, and these are best discussed with a physician who specializes in liver diseases. When treatment is successful, liver scarring and the potential for liver cancer are reduced.

What vitamins cure hepatitis B?

Some studies have shown that vitamin D by affecting TLR 2 expression can increase receptor expression, which in turn can inhibit the HBV virus in the early stages of the disease.

What is the upcoming Hep B cure?

A promising future – In summary, Bepirovirsen is a drug with very promising results for the cure of chronic hepatitis B and studies are being carried out combining Bepirovirsen with other therapies (pegylated interferon, vaccine, PAPD5 and PAPD7 enzyme inhibitors) to increase the efficacy of the drug treatment.

Why HBV Cannot be cured?

Abstract – Current treatments against chronic hepatitis B (CHB) include pegylated interferon alpha (Peg-IFNα) and nucleos(t)ide analogs (NAs), the latter targeting the viral retrotranscriptase, thus inhibiting de novo viral production. Although these therapies control infection and improve the patient’s quality of life, they do not cure HBV-infected hepatocytes.

A complete HBV cure is currently not possible because of the presence of the stable DNA intermediate covalently closed circular DNA (cccDNA). Current efforts are focused on achieving a functional cure, defined by the loss of Hepatitis B surface antigen (HBsAg) and undetectable HBV DNA levels in serum, and on exploring novel targets and molecules that are in the pipeline for early clinical trials.

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The likelihood of achieving a long-lasting functional cure, with no rebound after therapy cessation, is higher using combination therapies targeting different steps in the hepatitis B virus (HBV) replication cycle. Novel treatments and their combinations are discussed for their potential to cure HBV infection, as well as exciting new technologies that could directly target cccDNA and cure without killing the infected cells.

How close are we to cure hepatitis B?

There Is No Cure for Chronic Hepatitis B.

Can you have hepatitis B forever?

What is hepatitis B? – Hepatitis B is a liver infection caused by the hepatitis B virus. Some people with hepatitis B are sick for only a few weeks (known as “acute” infection), but for others, the disease progresses to a serious, lifelong illness known as chronic hepatitis B.

Can hepatitis B be cured in future?

With the momentum growing around hepatitis B drug discovery research, how far are we from a cure? Closer than ever, according to Timothy Block, PhD, president and co-founder of the Hepatitis B Foundation and its research arm, the Baruch S. Blumberg Institute. He points out that hepatitis C, initially thought to be incurable, can now be cured with new combination treatments. “Hepatitis B is in a similar position,” Block believes. And the need for a cure has never been greater, with over 240 million people living with chronic hepatitis B infection worldwide, resulting in 1 million deaths per year from related liver failure and liver cancer.

  1. Treatments are available,” explains Block, “but we have become a little too comfortable with the seven medications that are currently approved for use.” While these drugs are effective, the interferons have many side effects and the oral antivirals require lifelong use.
  2. Moreover, they work in only about half of the infected population, and reduce the rate of death due to liver disease by only about 40 to 70 percent.

For those who benefit from treatment, the antiviral drugs prove that medications can be effective. However, there are millions who do not benefit and are still left vulnerable. “We should not accept that a significant number of people will still die from hepatitis B-related complications despite taking the current drugs,” Block declares.

What would a cure look like? The current antiviral agents are similar and combinations do not offer any advantage. They have limited effectiveness against cccDNA, the seemingly indestructible “mini-chromosome” of the hepatitis B virus that continues to produce virus particles in infected liver cells, even in people being treated.

A cure, therefore, would have to destroy or silence cccDNA and provide long-term protective immunity. Because one-drug treatments can lead to drug resistance, a cure would almost certainly involve combination therapy. With the recent advances in hepatitis B research, scientists are optimistic that another big leap in the search for a cure is possible if other complementary drugs can be found.

  1. The Baruch S.
  2. Blumberg Institute of the Hepatitis B Foundation is at the forefront of research efforts to discover such new drugs.
  3. Blumberg Institute at the forefront Blumberg scientists have played a key role in increasing understanding of the virus life cycle and are recognized leaders in drug discovery research that also includes designing and developing assays to screen for new drugs.

“With our Drexel University colleagues, we are among the first, if not the only group, to identify a small molecule that inhibits hepatitis B virus cccDNA formation,” Block notes. This is significant because inhibition of cccDNA is considered essential in achieving a complete cure.

  • Block is confident that a drug with this mechanism will eventually become available.
  • In 2015, the Blumberg Institute licensed several of its discoveries to Arbutus Biopharma, the first company solely dedicated to hepatitis B drug discovery, and signed a three-year research agreement to work on novel approaches to developing a hepatitis B cure.

“This unique partnership will allow us to move our discoveries more rapidly from the lab to the clinic,” Block explains. Adding to its drug arsenal, Blumberg researchers have used computer modeling to design and produce targeted drugs against hepatitis B and liver cancer.

In another innovative approach, researchers are screening plant and fungal extracts from its Natural Products Collection, donated by Merck & Co. in 2011, and have already discovered two potential drugs that are active against hepatitis B. Getting close to the finish line “There has never been more optimism than right now that a cure is within reach,” says Block.

“This is the goal of the Hepatitis B Foundation, so we are all very excited.” Blumberg researchers are building on recent discoveries that have heightened the momentum around finding a cure for hepatitis B and liver cancer: new screening methods to search for effective drugs; new ways to treat hepatitis B using different approaches to shut down the virus; a new blood biomarker that aids in the early detection of liver cancer; and a promising drug that selectively kills liver cancer cells in animal studies.

“The years that we all have spent working towards a cure for hepatitis B have laid the groundwork for this final phase,” said Block. “We are committing everything we have, every resource at our disposal, to developing the therapies that will ultimately improve the lives of all people living with hepatitis B worldwide and ultimately relegate hepatitis B to the history books.” Baruch S.

Blumberg Institute HBV Research Pipeline The Baruch S. Blumberg Institute (BSBI) of the Hepatitis B Foundation is leading the charge in developing innovative new therapies against hepatitis B. Among the products in the pipeline: cccDNA Inhibitors We are among the first, if not the only group, to identify the first small molecule inhibitor of HBV cccDNA, which has now been made highly active and is licensed to Arbutus Biopharma for further development.

  • Capsid Inhibitors, “YES Kinase” Inhibitors We are using high-throughput screens and computer modeling to design and produce targeted drugs that include capsid inhibitors for HBV and “YES kinase” inhibitors for liver cancer.
  • Immune System Activators We have developed a new HBV drug that works by activating an infected liver cell’s own immune system, which has been shown to be effective in animal studies.

Natural Antiviral Agents We have screened thousands of plant and fungal extracts from our extensive Natural Products Collection and identified two new leads that show potential activity against HBV.

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Is Hep B always chronic?

Hepatitis B | CDC Hepatitis B is a vaccine-preventable liver infection caused by the hepatitis B virus (HBV). Hepatitis B is spread when blood, semen, or other body fluids from a person infected with the virus enters the body of someone who is not infected.

  1. This can happen through sexual contact; sharing needles, syringes, or other drug-injection equipment; or during pregnancy or delivery.
  2. Not all people newly infected with HBV have symptoms, but for those that do, symptoms can include fatigue, poor appetite, stomach pain, nausea, and jaundice.
  3. For many people, hepatitis B is a short-term illness.

For others, it can become a long-term, chronic infection that can lead to serious, even life-threatening health issues like liver disease or liver cancer. Age plays a role in whether hepatitis B will become chronic. The younger a person is when infected with the hepatitis B virus, the greater the chance of developing chronic infection.

About 9 in 10 infants who become infected go on to develop life-long, chronic infection. The risk goes down as a child gets older. About one in three children who get infected before age 6 will develop chronic hepatitis B. By contrast, almost all children 6 years and older and adults infected with the hepatitis B virus recover completely and do not develop chronic infection.

The best way to prevent hepatitis B is to get vaccinated. All adults aged 18-59 should receive the vaccine and any adult who requests it may get the vaccine. All adults 18 years and older should get screened at least once in their lifetime. : Hepatitis B | CDC

How does Omega 3 help hepatitis B?

Abstract – Omega-3 fatty acid supplemented total parenteral nutrition improves the clinical outcome of patients undergoing certain operations; however, its benefits for patients with hepatitis type B virus (HBV)-associated hepatocellular carcinoma (HCC) who have undergone hepatectomy are still not clear. The aim of this study was to evaluate the effect of omega-3 fatty acid supplemented total parenteral nutrition on the clinical outcome of patients with HBV-associated HCC who underwent hepatectomy at our institution. A total of 63 patients with HBV-associated HCC who underwent hepatectomy were included in this study. These patients were randomly assigned to receive standard total parenteral nutrition (the control group, n = 31) or omega-3 fatty acid supplemented total parenteral nutrition (the omega-3 fatty acid group, n = 32) for at least 5 d. The study endpoints were the occurrence of infection-related complications, recovery of liver function and length of hospital stay. The results showed that the omega-3 fatty acid group had a lower infection rate (omega-3 fatty acid, 19.4% vs control, 43.8%, P < 0.05), a better liver function after hepatectomy: alanine transaminase (omega-3 fatty acid, 48.23±18.48 U/L vs control, 73.34±40.60 U/L, P < 0.01), aspartate transaminase (omega-3 fatty acid, 35.77±14.56 U/L vs control, 50.53±24.62 U/L, P < 0.01), total bilirubin (omega-3 fatty acid, 24.29±7.40 mmol/L vs control, 28.37±8.06 mmol/L, P < 0.05) and a shorter length of hospital stay (omega-3 fatty acid, 12.71±2.58 d vs control, 15.91±3.23 d, P < 0.01). The serum contents of IL-6 (omega-3 fatty acid, 23.98±5.63 pg/mL vs control, 35.55±7.5 pg/mL, P < 0.01) and TNF-α (omega-3 fatty acid, 4.43±1.22 pg/mL vs control, 5.96±1.58 pg/mL, P < 0.01) after hepatectomy were significantly lower in the omega-3 fatty acid group than those of the control group. In conclusion, administration of omega-3 fatty acid may reduce infection rate and improve liver function recovery in HBV-associated HCC patients after hepatectomy. This improvement is associated with suppressed production of proinflammatory cytokines in these patients. Keywords: hepatectomy; hepatocellular carcinoma; omega-3 fatty acids; total parenteral nutrition.

Can hepatitis B be cured in future?

With the momentum growing around hepatitis B drug discovery research, how far are we from a cure? Closer than ever, according to Timothy Block, PhD, president and co-founder of the Hepatitis B Foundation and its research arm, the Baruch S. Blumberg Institute. He points out that hepatitis C, initially thought to be incurable, can now be cured with new combination treatments. “Hepatitis B is in a similar position,” Block believes. And the need for a cure has never been greater, with over 240 million people living with chronic hepatitis B infection worldwide, resulting in 1 million deaths per year from related liver failure and liver cancer.

Treatments are available,” explains Block, “but we have become a little too comfortable with the seven medications that are currently approved for use.” While these drugs are effective, the interferons have many side effects and the oral antivirals require lifelong use. Moreover, they work in only about half of the infected population, and reduce the rate of death due to liver disease by only about 40 to 70 percent.

For those who benefit from treatment, the antiviral drugs prove that medications can be effective. However, there are millions who do not benefit and are still left vulnerable. “We should not accept that a significant number of people will still die from hepatitis B-related complications despite taking the current drugs,” Block declares.

What would a cure look like? The current antiviral agents are similar and combinations do not offer any advantage. They have limited effectiveness against cccDNA, the seemingly indestructible “mini-chromosome” of the hepatitis B virus that continues to produce virus particles in infected liver cells, even in people being treated.

A cure, therefore, would have to destroy or silence cccDNA and provide long-term protective immunity. Because one-drug treatments can lead to drug resistance, a cure would almost certainly involve combination therapy. With the recent advances in hepatitis B research, scientists are optimistic that another big leap in the search for a cure is possible if other complementary drugs can be found.

The Baruch S. Blumberg Institute of the Hepatitis B Foundation is at the forefront of research efforts to discover such new drugs. Blumberg Institute at the forefront Blumberg scientists have played a key role in increasing understanding of the virus life cycle and are recognized leaders in drug discovery research that also includes designing and developing assays to screen for new drugs.

“With our Drexel University colleagues, we are among the first, if not the only group, to identify a small molecule that inhibits hepatitis B virus cccDNA formation,” Block notes. This is significant because inhibition of cccDNA is considered essential in achieving a complete cure.

Block is confident that a drug with this mechanism will eventually become available. In 2015, the Blumberg Institute licensed several of its discoveries to Arbutus Biopharma, the first company solely dedicated to hepatitis B drug discovery, and signed a three-year research agreement to work on novel approaches to developing a hepatitis B cure.

“This unique partnership will allow us to move our discoveries more rapidly from the lab to the clinic,” Block explains. Adding to its drug arsenal, Blumberg researchers have used computer modeling to design and produce targeted drugs against hepatitis B and liver cancer.

  • In another innovative approach, researchers are screening plant and fungal extracts from its Natural Products Collection, donated by Merck & Co.
  • In 2011, and have already discovered two potential drugs that are active against hepatitis B.
  • Getting close to the finish line “There has never been more optimism than right now that a cure is within reach,” says Block.
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“This is the goal of the Hepatitis B Foundation, so we are all very excited.” Blumberg researchers are building on recent discoveries that have heightened the momentum around finding a cure for hepatitis B and liver cancer: new screening methods to search for effective drugs; new ways to treat hepatitis B using different approaches to shut down the virus; a new blood biomarker that aids in the early detection of liver cancer; and a promising drug that selectively kills liver cancer cells in animal studies.

“The years that we all have spent working towards a cure for hepatitis B have laid the groundwork for this final phase,” said Block. “We are committing everything we have, every resource at our disposal, to developing the therapies that will ultimately improve the lives of all people living with hepatitis B worldwide and ultimately relegate hepatitis B to the history books.” Baruch S.

Blumberg Institute HBV Research Pipeline The Baruch S. Blumberg Institute (BSBI) of the Hepatitis B Foundation is leading the charge in developing innovative new therapies against hepatitis B. Among the products in the pipeline: cccDNA Inhibitors We are among the first, if not the only group, to identify the first small molecule inhibitor of HBV cccDNA, which has now been made highly active and is licensed to Arbutus Biopharma for further development.

Capsid Inhibitors, “YES Kinase” Inhibitors We are using high-throughput screens and computer modeling to design and produce targeted drugs that include capsid inhibitors for HBV and “YES kinase” inhibitors for liver cancer. Immune System Activators We have developed a new HBV drug that works by activating an infected liver cell’s own immune system, which has been shown to be effective in animal studies.

Natural Antiviral Agents We have screened thousands of plant and fungal extracts from our extensive Natural Products Collection and identified two new leads that show potential activity against HBV.

What is the elimination of 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.

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. Many people with hepatitis A, B, C, D or E exhibit only mild symptoms or no symptoms at all. 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.

  1. It is advised to avoid unnecessary medications due to the negative effect on liver function caused by these infections.
  2. Hepatitis C (HCV) can cause both acute and chronic infection.
  3. 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.