Thursday, May 19, 2022

New Cure For Hepatitis B

How Do Doctors Treat The Complications Of Autoimmune Hepatitis

Clinical trial investigates possibility of stopping medication as cure for Hepatitis B

If autoimmune hepatitis leads to cirrhosis, doctors can treat health problems and complications related to cirrhosis with medicines, surgery, and other medical procedures. If you have cirrhosis, you have a greater chance of developing liver cancer. Your doctor may order an ultrasound or other types of imaging tests to check for liver cancer.

If autoimmune hepatitis causes acute liver failure or cirrhosis with liver cancer or liver failure, you may need a liver transplant.

How Do Doctors Treat Autoimmune Hepatitis

Doctors treat autoimmune hepatitis with medicines that suppress, or decrease the activity of, your immune system, reducing your immune systems attack on your liver. The medicines doctors most often prescribe are corticosteroidsprednisone or prednisolonewith or without another medicine called azathioprine.

Doctors typically start with a relatively high dose of corticosteroids and then gradually lower the dose. Your doctor will try to find the lowest dose that works for you. Your doctor will use blood tests to find out how you are responding to the treatment. A decrease in levels of the liver enzymes alanine transaminase and aspartate transaminase shows a response to treatment. ALT and AST falling to normal levels shows a full response. In some cases, a doctor may repeat a liver biopsy to confirm the response to treatment and find out whether the damage has resolved.

Treatment can relieve symptoms and prevent or reverse liver damage in many people with autoimmune hepatitis. Early treatment of autoimmune hepatitis can lower the chances of developing cirrhosis and other complications. A minority of people who have no symptoms or only a mild form of the disease may or may not need medicines.

Do Medicines Used To Treat Autoimmune Hepatitis Have Side Effects

Medicines for autoimmune hepatitis can cause side effects. Your doctor will monitor any side effects and help you manage them while you take these medicines. Your doctor also may adjust the doses or change the medicines you take. You may need to stop taking corticosteroids or azathioprine if you have severe side effects.

Side effects of corticosteroids may include

  • changes in how you look, which may include weight gain, a fuller face, acne, or more facial hair
  • liver damage
  • pancreatitis

Corticosteroids and azathioprine suppress, or decrease the activity of, your immune system, which increases your risk for infections. These medicines can also increase your risk of developing cancers, especially skin cancers.

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National Institutes Of Health Recommendations

The National Institutes of Health recommends nucleoside therapy for the treatment of patients with acute liver failure, as well as cirrhotic patients who are HBV DNA positive and those with clinical complications, cirrhosis or advanced fibrosis with positive serum HBV DNA, or reactivation of chronic HBV during or after chemotherapy or immunosuppression. In addition, immunoglobulin and vaccination should be administered to newborns born to women positive for hepatitis B surface antigen .

In general, for hepatitis B e antigen -positive patients with evidence of chronic HBV disease, treatment is advised when the HBV DNA level is at or above 20,000 IU/mL and when serum ALT is elevated for 3-6 months.

For HBeAg-negative patients with chronic hepatitis B disease, treatment can be administered when the HBV DNA is at or above 2,000 IU/mL and the serum ALT is elevated for 3-6 months.

In patients coinfected with HBV and HIV, initiate therapy against HBV and administer antiretroviral therapy as well.

The NIH also indicates that immediate therapy is not routinely indicated for patients who have the following :

  • Chronic hepatitis B with high levels of serum HBV DNA but normal serum ALT levels or little activity on liver biopsy

  • Low levels of or no detectable serum HBV DNA and normal serum ALT levels

  • Positive serum HBV DNA but not HBsAg , unless the patient is undergoing immunosuppression

Treatment For Chronic Hepatitis B

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If blood tests show that you still have hepatitis B after 6 months, your doctor may recommend medication to reduce the risk of complications of hepatitis B and regular tests to assess the health of your liver.

Treatment is usually offered if:

  • your immune system is unable to control the hepatitis B by itself
  • there’s evidence of ongoing liver damage

Hepatitis B medications can help keep the virus under control and stop it damaging your liver, although they will not necessarily cure the infection and some people need lifelong treatment.

The main medicines for chronic hepatitis B include peginterferon alfa 2-a and antiviral medicines.

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Hepatitis B: A New Weapon Against An Old Enemy

volume 27, pages 16721673

  • 1881 Accesses

    New strategies based on nucleic acid technologies are being exploited to treat chronic hepatitis Ba pilot clinical study of antisense oligonucleotide treatment shows the potential promise of this approach.

    Chronic infection with hepatitis B virus afflicts more than 250 million people worldwide. Effective vaccines and treatments that potently suppress viral levels and reduce liver inflammation have been available for over 20 years, but infection with HBV continues to exact a heavy public-health toll. The goal of a cure for chronic infection with HBV remains elusive. At present, nucleoside analogs and interferon- are the only approved therapies, and they rarely cure the infection. Even in patients with serological recovery and HBV DNA, with normal liver tests), HBV can persist in small quantities and can be reactivated when host antiviral immunity is perturbed. However, most people with serological recovery have few or no clinical consequences thus, the current development of therapeutics against HBV is focused on achieving this state the so-called functional cure through various pharmacological approaches. In this issue of Nature Medicine, Yuen et al. describe the application of antisense oligonucleotide technology to suppress HBV replication in patients with chronic infection with HBV.

    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.

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    Scientists Simulate Step In Hepatitis B Viral Infection To Help Develop Therapies Targeted At Capsid Disassembly

    by Tejas Mahadevan Padmanabhan, Beckman Institute for Advanced Science and Technology

    With up to 2.4 million U.S. cases and over 250 million chronic cases globally, hepatitis B infection persists despite the availability of a vaccine. Vaccines work by immunizing the body against a virus to prevent infection however, there is no cure for individuals who do become infected . Hepatitis B infection can lead to liver damage and even cancer, posing a threat to public health.

    Understanding the fundamental steps of viral infection can help design drugs to interrupt these processes and prevent chronic infection. With this rationale, researchers from the Beckman Institute and the Department of Chemistry modeled the process of capsid disassembly of the hepatitis B virus at an unprecedented atomic level.

    The team included Zhaleh Ghaemi, the study’s lead author and a research scientist in chemistry Emad Tajkhorshid, a professor of biochemistry and Martin Gruebele, a professor of chemistry. Their paper, titled “Molecular mechanism of capsid disassembly in hepatitis B virus,” is published in PNAS.

    “Over the past few decades, the developments of advanced simulation software such as NAMD, developed here at UIUC, and a more accurate treatment of interactions between atoms, enabled us to simulate a system of this size and complexity,” Ghaemi said.

    Armed with cutting-edge computational capabilities, the team pried apart the hepatitis B viral capsid disassembly process.

    Explore further

    Durability And Related Factors After Hbsag Clearance

    Treatment of Hepatitis B 2019: Easy to Treat, Hard to Understand!

    When patients with HBeAg-positive CHB achieve a satisfactory antiviral treatment endpoint , the clinical recurrence is 2040%, and the virological recurrence can be as high as 8090% after drug withdrawal . Because the safety of drug withdrawal is uncertain, HBsAg clearance is recommended as the ideal treatment endpoint for CHB patients. The accessibility and rate of HBsAg clearance was mentioned above, but the durability of HBsAg clearance after treatment cessation remains controversial.

    HBeAg status should also receive attention in the pursuit of HBsAg clearance. The clearance of HBsAg in most patients is based on HBV DNA suppression and HBeAg seroconversion, but a few patients exhibit different HBsAg response patterns, such as HBsAg clearance without HBeAg seroconversion. Only HBsAg clearance based on HBV DNA suppression and HBeAg seroconversion is safe for drug withdrawal .

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    Disease Affecting 257 Million People Needs Better Treatment

    This article is a collaboration between MedPage Today and:

    VIENNA The International Liver Conference kicked off here today with a push to find a cure not just maintenance treatment for the one quarter billion people living with hepatitis B virus infection, but researchers said that finding a cure could be elusive, and it certainly won’t come quickly.

    “I think we are still at least 3 years away from starting a Phase III clinical trial that would probably include a combination therapy,” said Massimo Levrero, PhD, a member of the governing body of the International Coalition to Eliminate HBV and director of the Cancer Research Centre of Lyon in France.

    Levrero, one of several participants in a press conference at the start of the 5-day annual meeting of the European Association for the Study of the Liver, told MedPage Today that there are numerous drug treatment candidates being tested to attack various structures of the virus, but he compared HBV to HIV rather than hepatitis C virus for which an 8-week functional cure is now available.

    “Hepatitis B is very different than hepatitis C, and it is very difficult to eradicate, as is HIV,” he said.

    He noted that antivirals can suppress the virus but do not affect the risk of causing liver cancer. Levrero said that when people have to take drugs for long periods of time sometimes decades in the case of HBV treatment there is a waning of compliance, which makes the need for a cure more imperative.

    The Time To Cure Hepatitis B Is Now

    Nature Reviews commentary lays groundwork for the momentum behind hepatitis B cure research

      On the eve of World Hepatitis Day, the International Coalition to Eliminate HBV , a global group of researchers, patient representatives and health organisations, has called for the integration of a hepatitis B cure in global plans to eliminate viral hepatitis.

      More than 290 million people worldwide are chronically infected with the HBV, a viral infection that attacks the liver and can cause both acute and chronic disease. Last year, nearly 900 000 people died from the disease.

      A safe and effective vaccine to prevent HBV infection exists and its universal delivery is essential for the elimination of HBV as a public health threat. Lifelong treatment is also needed for those already chronically infected but currently is only accessed by some five per cent of the 94 million people who need it.

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      Finding A Cure For Hepatitis B: Asia

      On 29 July 2021 for World Hepatitis Day ICE HBV, together with Coalition to Eradicate Viral Hepatitis in Asia Pacific and Yellow Warriors Society Philippines, Inc. , co-hosted the webinar Finding a Cure for Hepatitis B: Asia-Pacific Regional Webinar. An event aimed discussing the latest research in HBV Cure and surrounding topics with people living with HBV and their community.

      Speakers were Dee Lee, Inno Community Development Organisation, China, Lien Tran, Doherty Institute Melbourne, Margaret Hellard, Burnet Institute, Melbourne, and Seng Gee Lim, National University Health System, Singapore.

      With The Momentum Growing Around Hepatitis B Drug Discovery Research We Are Closer Than Ever To A Cure

      Why do newborns need the hepatitis B vaccine?

      From the Spring 2016 B Informed Newsletter

      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?

      cccDNA Inhibitors

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      Nucleocapsid Assembly Inhibitors And Core Inhibitors

      The HBV core protein plays a central role in the viral replication cycle starting with uncoating and release of rcDNA, delivery to the nuclear pore basket, nucleocapsid formation and packaging of pgRNA, and finally interaction with HBsAg during the end stages of morphogenesis. There is indirect evidence that the protein binds to cellular promoters and regulates gene expression . In this respect it constitutes another attractive antiviral target.

      The following two classes of core protein allosteric modulators have been discovered: the heteroaryldihydropyrimidines and the phenylpropenamides , sulfamoylbenzamides, and several other chemotypes .

      HAP derivatives, misdirect core protein dimers to assemble aberrant non-capsid polymers, leading to the degradation of the core protein . GLS4 is a representative compound of the HAP family.

      Type II CpAMs were found to accelerate formation of capsid assembly, possibly at an inappropriate time and place, thereby preventing pgRNA encapsidation and, instead, inducing the assembly of empty capsids .

      In vitro, GLS4 inhibited virus accumulation in the supernatant of hepatic cell lines. This was tested in vivo in nude mice inoculated with HepAD38 cells, which then grew out as tumors, resulting in viremia. Treatment of mice with GLS4 and BAY 41-4109 caused a strong and sustained drop in HBV DNA to about the same extents both during and after treatment .

      Living With Hepatitis B

      If you have hepatitis, you should:

      • avoid having unprotected sex, including anal and oral sex, unless you’re sure your partner has been vaccinated against hepatitis B
      • avoid sharing needles used to inject drugs with other people
      • take precautions to avoid the spread of infection, such as not sharing toothbrushes or razors with other people
      • eat a generally healthy, balanced diet there’s no special diet for people with hepatitis B
      • avoid drinking alcohol this can increase your risk of developing serious liver problems
      • speak to your doctor if you’re thinking of having a baby

      People with hepatitis B can usually have a healthy pregnancy, but it’s a good idea to discuss your plans with a doctor first as you may need extra care and your medications may need to be changed.

      There’s a risk of pregnant women with hepatitis B passing the infection on to their child around the time of the birth, but this risk can be reduced by ensuring the baby is vaccinated shortly after they’re born.

      Page last reviewed: 30 January 2019 Next review due: 30 January 2022

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      Accessibility And Hbsag Clearance Rate

      HBsAg clearance occurs spontaneously or via antiviral treatment in CHB patients. The most commonly used drugs are nucleoside analogue and pegylated interferon . NA drugs include entecavir , tenofovir disoproxil fumarate and tenofovir alafenamide fumarate . The 2018 AASLD guidelines recommend Peg-IFN, ETV, or TDF as the preferred initial therapy for adults with immune-active CHB. It also suggests that alanine transaminase levels be tested at least every 6 months for adults with immune-tolerant CHB to monitor for potential transition to immune-active or immune-inactive CHB . The 2017 EASL guideline recommends ETV, TDF and TAF as the preferred monotherapy regimens, and the extension of the duration of Peg-IFN therapy beyond week 48 may be beneficial in selected HBeAg-negative CHB patients . The potential side effects of NAs include lactic acidosis for ETV and nephropathy, osteomalacia, lactic acidosis for TDF. CHB patients should be clinically monitored. The most frequently reported side effects for Peg-IFN are flu-like syndrome, myalgia, fatigue, mood disturbances, weight loss, hair loss and local reactions at the site of injection, and these side effects may be partially managed with dose reduction . Currently, the clearance of HBsAg is based primarily on sequential or combined treatment with NA and Peg-IFN.

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