Friday, May 20, 2022

Cure For Chronic Hepatitis B

What Treatments Are Available For Chronic Hepatitis B If Medications Dont Work

Hepatitis B: Treatment and care for a chronic condition

If you have advanced hepatitis B, you might also become a candidate for a liver transplant. This path does not always result in a cure because the virus continues in your bloodstream after a transplant. To prevent being infected again after your transplant, you may be prescribed hepatitis B immunoglobulin with an antiviral agent.

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Infection Cured In Mice

The scientists therefore had to go one step further: We then combined the siRNA method with a therapeutic vaccination developed by us. This enabled us to trigger a strong immune response against the virus. This led to cure of hepatitis B virus infection in two different mouse models, explains Dr. Thomas Michler, physician and one of the two first authors of the study.

We are very pleased that for the clinical trials of TherVacB we are able to cooperate with a consortium of Europes leading virologists, immunologists and hepatologist, guided by Helmholtz Zentrum München, adds Protzer. The consortium will receive funding of more than 10 million from the European Union within the program Horizon 2020 .

Future Directions To Improve Hbv Therapeutic Vaccination Strategies

Several strategies have promise to improve the efficacy of therapeutic vaccination in chronic HBV . Consistently, HBV vaccine candidates do not seem to induce strong HBV-specific T cell responses when administered to people with chronic HBV, even when they are shown to be immunogenic in healthy individuals . Potential approaches to improve therapeutic vaccination, therefore, all attempt to augment vaccine-induced T cell responses and overcome the HBV-specific T cell dysfunction associated with chronic infection.

FIGURE 2

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How Is It Transmitted

Hepatitis B is highly infectious, and is spread from one person to another through exposure to infected blood and body fluids . It can be spread through:

  • blood transfusions or organ transplantation in countries where blood or blood products have not been properly screened for hepatitis B and other viruses transmitted through blood
  • unprotected sex with an infected person
  • sharing needles or equipment for injecting drugs
  • unsterilized medical/dental equipment and shared/contaminated materials or equipment used for tattooing, body piercing or acupuncture
  • sharing toothbrushes or razors
  • childbirth
  • household contact between family members

The Hepatitis B Vaccine

Push to cure hepatitis B, a neglected disease

The hepatitis B vaccine is one of the most effective ways to prevent hepatitis B. Its usually divided into three doses, which are given over the course of six months. In many countries, infants receive their first dose of the vaccine at birth.

The Centers for Disease Control recommends that all children under the age of 19 be vaccinated if they havent already received the vaccination. Adults can also get the hepatitis B vaccine, and its generally recommended if you have an increased risk of infection due to:

  • traveling to or living in a region where hepatitis B is common
  • being sexually active with more than one partner
  • working in a medical setting
  • using intravenous drugs

If youve been exposed to the hepatitis B virus and havent been vaccinated, try to see a doctor right away. They can administer the first dose of the vaccine, though youll need to follow up to receive the remaining doses over the next few months.

They can also prescribe a medication called

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Hbv Optimizing Patient Selection Lowering Hbv Antigen Load

High levels of HBsAg are thought to contribute to the HBV-specific T cell dysfunction in chronic HBV . Quantitative HBsAg measures serum HBsAg transcribed from HBV cccDNA, as well as HBV DNA integrated into the host genome . In patients with suppressed circulating HBV DNA on nucleoside therapy quantitative HBsAg levels remain elevated, despite reduced HBV replication. In these individuals, integrated HBV DNA is the most important source of HBsAg .

How Long Does It Last

According to the World Health Organization , the complete vaccine series induces protective antibody levels in of the infants, children, and adolescents who receive it.

Immune memory induced by the HBV vaccine can last for in healthy people. That said, studies into the duration of the protection that the vaccine offers are ongoing.

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Treatment Options For Hepatitis B

People living with chronic hepatitis B infection should expect to live a long and healthy life. There are decisions people can make to protect their livers such as seeing a liver specialist or health care provider regularly, avoiding alcohol and tobacco, and eating healthy foods. There are also approved drugs for both adults and children that control the hepatitis B virus, which helps reduce the risk of developing more serious liver disease, but there is still no complete cure.

Current treatments for hepatitis B fall into two general categories:

  • Immune modulator Drugs These are interferon-type drugs that boost the immune system to help get rid of the hepatitis B virus. They are given as a shot over 6 months to 1 year.
  • Antiviral Drugs These are drugs that stop or slow down the hepatitis B virus from reproducing, which reduces the inflammation and damage of your liver. These are taken as a pill once a day for at least 1 year and usually longer.

It is important to know that not everyone with chronic hepatitis B infection needs to be treated. This can be difficult to accept when first diagnosed because taking a drug to get rid of the virus seems like the first step to getting better. Current treatments, however, are generally found to be most effective in those who show signs of active liver disease .

Hepatitis B Drug Watch

Visit the HBF Drug Watch for a complete list of the approved treatments for hepatitis B and promising new drugs in development.

Interferon And Hepatitis B: Current And Future Perspectives

Chronic Hepatitis B: Treatment Indications and Options (2/3)
  • 1Key Laboratory of Medical Molecular Virology , School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
  • 2Research Unit of Cure of Chronic Hepatitis B Virus Infection, Chinese Academy of Medical Sciences, Shanghai, China

Chronic hepatitis B virus infection remains a major health burden worldwide for which there is still no effective curative treatment. Interferon consists of a group of cytokines with antiviral activity and immunoregulatory and antitumor effects, that play crucial roles in both innate and adaptive immune responses. IFN- and its pegylated form have been used for over thirty years to treat chronic hepatitis B with advantages of finite treatment duration and sustained virologic response, however, the efficacy is limited and side effects are common. Here, we summarize the status and unique advantages of IFN therapy against CHB, review the mechanisms of IFN- action and factors affecting IFN response, and discuss the possible improvement of IFN-based therapy and the rationale of combinations with other antiviral agents in seeking an HBV cure.

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New Strategy To Cure Chronic Hepatitis B Infection

by Karolinska Institutet

Scientists from Karolinska Institutet and Hannover Medical School have published two studies that provide insights into how the immune system responds and helps to clear a hepatitis B infection after treatment interruption. The findings offer a framework for future tailored treatment strategies and are published in the Journal of Infectious Diseases and Journal of Hepatology.

Chronic hepatitis B caused by hepatitis B virus , affects 250 million individuals worldwide. The virus infects the liver and infected patients are at risk of developing liver cirrhosis and liver cancer.

Nucleoside/nucleotide analogues are the most commonly used drugs to treat CHB, but this treatment only suppresses the virus and rarely leads to eradication of the infection. Thus, for most patients this is a life-long treatment.

The immune system recovers in some patients

Because of this, new treatment strategies are continuously evaluated with the aim to achieve elimination of HBV. One involves doing a structured NA treatment interruption in patients that have been on the treatment for a couple of years. In 20-30 per cent of the CHB patients the immune system recovers from being exhausted by the chronic infection and gains the capacity to efficiently fight the virus when it starts to replicate after the treatment has been discontinued.

Further studies necessary

Explore further

Targeting T Cells To The Liver

Maximizing effective HBV-specific T cells at the site of infection might also be critical in inducing HBV functional cure. Resident memory T cells have been shown to be key for local control of HBV in the liver . A primeâpull vaccination strategy which employs intramuscular delivery of a simian adenoviral vector to prime T cells in the periphery, followed by an intravenous boost of MVA-vectored vaccine to pull T cells into the liver, was shown to be effective in protecting mice from the liver stage of malaria . This strategy also increased the magnitude of HBV-specific T cells in the liver at peak time-point after boost MVA vaccination in mice , but its effectiveness at inducing HBV functional cure remains to be tested. These data support that, for hepatotrophic pathogens, it is critical to understand the T cell response in the liver in order to optimize vaccine efficacy. This has not been attempted routinely in human vaccine studies due to the invasiveness of liver biopsy. Recently, however, fine-needle aspiration has been shown to be a safe alternative to biopsy that enables serial assessment of local liver immunology . Future clinical studies should consider FNA as routine to evaluate the intrahepatic response to vaccination which can inform and optimize vaccine development.

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Who Is At Risk For Hepatitis B

Anyone can get hepatitis B, but the risk is higher in:

  • Infants born to mothers who have hepatitis B
  • People who inject drugs or share needles, syringes, and other types of drug equipment
  • Sex partners of people with hepatitis B, especially if they are not using latex or polyurethane condoms during sex
  • Men who have sex with men
  • People who live with someone who has hepatitis B, especially if they use the same razor, toothbrush, or nail clippers
  • Health care and public-safety workers who are exposed to blood on the job

If you have chronic hepatitis B, you may not have symptoms until complications develop. This could be decades after you were infected. For this reason, hepatitis B screening is important, even if you have no symptoms. Screening means that you are tested for a disease even though you donât have symptoms. If you are at high risk, your health care provider may suggest screening.

Adaptive Immune Responses Are Necessary For Clearance Of Acute Hbv

Push to cure hepatitis B, a neglected disease

Studies of the immune response in acutely infected individuals that go on to resolve HBV consistently show robust CD8 and CD4 T cell responses towards regions of HBV proteins, including core, polymerase and surface . Ex-vivo, these cells appear functional, producing proinflammatory cytokines such as interferon -γ) on restimulation with recombinant HBV antigens or peptides. CD8 but not CD4 T cell depletion in HBV-infected non-human primates disrupts viral elimination , demonstrating that CD8 T cells are necessary to resolve acute infection, largely through non-cytopathic mechanisms .

HBV surface-specific B cells are also important in acute HBV infection. Anti-hepatitis B surface antigen antibodies neutralize HBsAg and contribute to sustained HBsAg loss, which defines resolution of acute HBV infection .

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Hepatitis B And Pregnancy

The American College of Obstetricians and Gynecologists , the US Preventive Services Task Force , and the World Health Organization recommend routine prenatal screening for hepatitis B surface antigen in all pregnant womenduring every pregnancyregardless of previous test results or vaccinations. Pregnant women at risk for hepatitis B infections should be specifically targeted for vaccination. The risk of transmission of hepatitis B associated with amniocentesis is low. WHO further recommends all pregnant women undergo testing at least once for HIV and syphilis in addition to that for HBsAg and as early as possible in the pregnancy.

It is recommended that all infants receive their first dose of hepatitis B vaccine as soon as possible after birth , followed by two or three doses to complete the primary series.

To prevent maternal-fetal HBV transmission, a conditional WHO recommendation is that HBsAg-positive gravida who have an HBV DNA 5.3 log10 IU/mL receive tenofovir prophylaxis beginning the 28th week of pregnancy until at least birth. This is in addition to the three-dose hepatitis B vaccination in all infants, including a timely birth dose. When antenatal HBV DNA testing is not available, HBeAg testing can be used as an alternative study to determine eligibility for tenofovir prophylaxis to prevent mother-to-child transmission of HBV.

What Are The Symptoms

  • Symptoms can take 2 to 6 months to appear.
  • Many people who are infected with hepatitis B have either no symptoms or only mild symptoms.
  • Symptoms of acute hepatitis B can include fatigue, loss of appetite, joint pain, abdominal pain, nausea, vomiting, fever, and dark urine. A small number of people will develop jaundice .
  • Some people develop chronic hepatitis B and most remain contagious for the rest of their lives. Chronic infection may lead to cirrhosis and/or liver cancer. Most people with chronic hepatitis B are unaware of their infection.

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When Should I Contact A Health

Any infant, child, or adult that has not been vaccinated against HBV should be vaccinated especially if they have had any close association with HBV-infected individuals.

An individual with chronic hepatitis B infection is advised to

  • have follow-up every 6-12 months to maximize their health,
  • get vaccinated against hepatitis A, and

Discuss diet, lifestyle changes, and ways to prevent transmission of their disease to others with your health-care professional.

Emergency Hepatitis B Treatment

Chronic Hepatitis B: Treatment Indications and Options (3/3)

See your GP as soon as possible if you think you may have been exposed to the hepatitis B virus.

To help stop you becoming infected, they can give you:

  • a dose of the hepatitis B vaccine you’ll also need 2 further doses over the next few months to give you long-term protection
  • hepatitis B immunoglobulin a preparation of antibodies that work against the hepatitis B virus and can offer immediate but short-term protection until the vaccine starts to take effect

These are most effective if given within 48 hours after possible exposure to hepatitis B, but you can still have them up to a week after exposure.

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What Is The Treatment For Hepatitis B

Prevention is recommended by receiving a vaccine for HBV.

Receiving an injection of the hepatitis B immune globulin within 12 hours of coming in contact with the virus may help prevent the development of the disease.

At present, there is no specific treatment for patients with acute hepatitis B. Acute infection is usually short and will often resolve on its own. Your health care provider may recommend rest, and adequate nutrition and fluids to help your body fight the infection. Hospitalization may be required for patients who suffer from severe vomiting and who are unable to maintain adequate nutritional levels. It may also be required to prevent the development of complications.

While chronic infection cannot be cured, there are two standard treatments in Canada that may control the virus and prevent further damage to the liver.

  • Antiviral medications can fight the virus and slow damage to the liver.
  • Interferon which may be given for short periods and if effective, results in suppression of the virus.

Strategies To Improve The Efficacy Of Ifn

Given the unique advantages of but relatively low response rates to IFN therapy, there is an urgent need to improve its efficacy .

Figure 1 Predictors and strategies for improvement of the efficacy of IFN-based therapy for chronic hepatitis B.

In addition to type I IFN, type III IFNs, consisting of four IFN- subtypes , has been considered as an alternative in treatment of CHB . IFN-III signals through a heterodimeric receptor composed of IFN- receptor-1 and interleukin-10 receptor subunit beta . IFNLR1 is expressed primarily on epithelial cells, such as hepatocytes, and on select immune cells, including pDCs and some B-lymphocytes, which may indicate better cell-type specific activity . One of the most impactful findings about IFN- is the strong association of IFN- polymorphisms with chronic HCV clearance during the acute stage of infection and of achieving HCV cure with IFN-I-based therapy in chronic infection . Unfortunately, the similar association cannot be identified in HBV patients with high confidence and good reproducibility among various studies . Although IFN- can activate IFN signaling pathways and lower HBV viral load, pegylated IFN-1 was less efficient than PEG-IFN-2 24 weeks post-treatment because fewer patients achieved HBeAg seroconversion .

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How Is Acute Hepatitis B Treated

Acute hepatitis B doesnt always require treatment. In most cases, a doctor will recommend monitoring your symptoms and getting regular blood tests to determine whether the virus is still in your body.

While you recover, allow your body to rest and drink plenty of fluids to help your body fight off the infection. You can also take an over-the-counter pain reliever, such as ibuprofen , to help with any abdominal pain you have.

See a doctor if your symptoms are severe or seem to be getting worse. You may need to take a prescription antiviral medication to avoid potential liver damage.

Like acute hepatitis B, chronic hepatitis B may not require medical treatment to avoid permanent liver damage. In some patients, monitoring symptoms and getting regular liver tests is appropriate.

Treatment generally involves antiviral medications, such as:

  • peginterferon alfa-2a injections
  • antiviral tablets, such as tenofovir or entecavir

Antiviral medications can help to reduce symptoms and prevent liver damage. But they rarely completely get rid of the hepatitis B virus. Instead, the goal of treatment is to have the lowest viral load possible. Viral load refers to the amount of a virus in a blood sample.

Theres no cure for hepatitis B, but the condition is easily preventable by taking a few precautions. Hepatitis B is often spread through sexual contact, shared needles, and accidental needle sticks.

You can reduce your risk of developing hepatitis B or spreading the virus to others by:

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