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Friday 16 November 2012

HEPATITIS B



The hepatitis B virus consists of a core containing DNA and a DNA polymerase enzyme needed for virus replication. The core of the virus is surrounded by surface protein . The virus, also called a Dane particle, and an excess of its surface protein (known as hepatitis B surface antigen) circulate in the blood. Humans are the only source of infection.


. Hepatitis B surface antigen (HBsAg) is a protein which makes up part of the viral envelope. Hepatitis B core antigen (HBcAg) is a protein which makes up the capsid or core part of the virus (found in the liver but not in blood). Hepatitis B e antigen (HBeAg) is part of the HBcAg which can be found in the blood and indicates infectivity.
Hepatitis B infection affects 300 million people and is one of the most common causes of chronic liver disease and hepatocellular carcinoma world-wide.
Hepatitis B may cause an acute viral hepatitis; however, the acute infection is often asymptomatic, particularly when acquired at birth. Many individuals with chronic hepatitis B are also asymptomatic. Chronic hepatitis, associated with elevated serum transaminases, may occur and can lead to cirrhosis, usually after decades of infection 
The risk of progression to chronic liver disease depends on the source of infection  Vertical transmission, from mother to child in the perinatal period, is the most common cause of infection world-wide and carries the highest risk.

 SOURCE OF HEPATITIS B INFECTION AND RISK OF CHRONIC INFECTION

Route of transmission Risk of chronic infection
Horizontal transmission 10%
Injection drug use  
Infected unscreened blood products  
Tattoos/acupuncture needles  
Sexual (homosexual and heterosexual)  
Vertical transmission 90%
HbsAg-positive mother  

There is an initial immunotolerant phase with high levels of virus and normal liver biochemistry. An immunological response to the virus then occurs, with elevation in serum transaminases which causes liver damage: chronic hepatitis. If this response is sustained over many years and viral clearance does not occur promptly, chronic hepatitis may result in cirrhosis. In individuals where the immunological response is successful, viral load falls, HBe antibody develops and there is no further liver damage. Some individuals may subsequently develop HBV-DNA mutants, which escape from immune regulation, and viral load again rises with further chronic hepatitis. Mutations in the core protein result in the virus's inability to secrete HBe antigen despite high levels of viral replication; such individuals have HBeAg-negative chronic hepatitis. (ALT = alanine aminotransferase; AST = aspartate aminotransferase)


 (HBsAg = hepatitis B surface antigen; anti-HBs = antibody to HBsAg; HBeAg = hepatitis B e antigen; anti-HBe = antibody to HBeAg; anti-HBc = antibody to hepatitis B core antigen)

 INTERPRETATION OF MAIN INVESTIGATIONS USED IN THE SEROLOGICAL DIAGNOSIS OF HEPATITIS B VIRUS INFECTION

    Anti-HBc  
Interpretation HBsAg IgM IgG Anti-HBs
Incubation period + + - -
Acute hepatitis
Early + + - -
Established + + + -
Established (occasional) - + + -
Convalescence
  (3-6 months) - ± + ±
  (6-9 months) - - + +
Post-infection
> 1 year - - + +
Uncertain - - + -
Chronic infection
Usual + - + -
Occasional - - + -
Immunisation without infection - - - +

+ positive; - negative; ± present at low titre or absent.
Investigations
Serology
HBV contains several antigens to which infected persons can make immune responses  these antigens and their antibodies are important in identifying HBV infection 
In acute infection the hepatitis B surface antigen (HBsAg) is a reliable marker of HBV infection, and a negative test for HBsAg makes HBV infection very unlikely but not impossible . HBsAg appears in the blood late in the incubation period and before the prodromal phase of acute type B hepatitis; it may be present for only a few days, disappearing even before jaundice has developed, but usually lasts for 3-4 weeks and can persist for up to 5 months.
Antibody to HBsAg (anti-HBs) usually appears after about 3-6 months and persists for many years or perhaps permanently. Anti-HBs implies either a previous infection, in which case anti-HBc (see below) is usually also present, or previous vaccination when anti-HBc is not present.
The hepatitis B core antigen (HBcAg) is not found in the blood, but antibody to it (anti-HBc) appears early in the illness and rapidly reaches a high titre which then subsides gradually but persists. Anti-HBc is initially of IgM type with IgG antibody appearing later. Anti-HBc (IgM) can sometimes reveal an acute HBV infection when the HBsAg has disappeared and before anti-HBs has developed (and 
The hepatitis B e antigen (HBeAg) appears only transiently at the outset of the illness and is followed by the production of antibody (anti-HBe). The HBeAg reflects active replication of the virus in the liver. The persistence of HBsAg for longer than 6 months indicates chronic infection.
Chronic HBV infection (see below) is marked by the presence of HBsAg and anti-HBc (IgG) in the blood. Usually, HBeAg or anti-HBe is also present; HBeAg indicates continued active replication of the virus in the liver while anti-HBe implies that replication is occurring at a much lower level or that HBV-DNA has become integrated into host hepatocyte DNA.
Viral load

 HBV-DNA encodes four proteins: a DNA polymerase needed for viral replication (P), a surface protein (S), a core protein (C) and an X protein. The pre-C and C regions encode a core protein and an e antigen. Although mutations in the hepatitis B virus are frequent occurrences, certain mutations have important clinical effects. Pre-C encodes a signal sequence needed for the C protein to be secreted from the liver cell into serum as e antigen. A mutation in the pre-core region leads to a failure of secretion of e antigen into serum and so individuals have high levels of viral production but no detectable e antigen in the serum. Mutations can also occur in the surface protein and may lead to the failure of vaccination (surface antibodies produced against native S protein) to prevent infection. Mutations also occur in the DNA polymerase during antiviral treatment with lamivudine.

HBV-DNA can be measured by polymerase chain reaction (PCR) in the blood. Viral loads are usually in excess of 105 copies/ml in the presence of active viral replication, as indicated by the presence of e antigen. In contrast, in those with low viral replication, HBsAg- and anti-HBe-positive, viral loads are less than 105 copies/ml. The exception is in patients who have a mutation in the pre-core protein, which means they cannot secrete e antigen into serum . Such individuals will be anti-HBe-positive but have a high viral load and often evidence of chronic hepatitis. These mutations are common in the Far East and those affected are classified as having e antigen-negative chronic hepatitis. They respond differently to antiviral drugs from those with classical e antigen-positive chronic hepatitis.
Measurement of viral load is important in monitoring antiviral therapy and identifying patients with pre-core mutants. Specific HBV genotypes can also be identified using PCR. Genotypes B and C appear to have more aggressive disease that responds less well to antiviral therapy.

Management

Acute hepatitis B

Treatment is supportive with monitoring for acute liver failure, which occurs in less than 1% of cases.
Chronic hepatitis B
Treatments are still limited, with no drug able to eradicate hepatitis B infection completely. The indication for treatment is a high viral load in the presence of active hepatitis, as demonstrated by elevated serum transaminases and/or histological evidence of inflammation.
Alfa-interferon
This is most effective in selected patients with a low viral load and serum transaminases greater than twice the upper limit of normal in whom it acts by augmenting a native immune response. In HBeAg-positive chronic hepatitis 33% lose e antigen after 4-6 months of treatment compared to 12% of controls. Response rates are lower in HBeAg-negative chronic hepatitis, even when patients are given longer courses of treatment. Interferon is contraindicated in the presence of cirrhosis as it may cause a flare in serum transaminases and precipitate liver failure. Longer-acting pegylated interferons which can be given once weekly have been evaluated in both HBeAg-positive and HBeAg-negative chronic hepatitis . Other antiviral therapies are required because many patients with chronic hepatitis B have high levels of viraemia and/or low transaminase levels and are not therefore candidates for interferon.
Lamivudine

PEGYLATED INTERFERONS IN CHRONIC HEPATITIS B INFECTION

'In HBeAg-positive chronic hepatitis treatment with pegylated interferon for 6 months eliminates HBeAg in 35%, and normalises liver biochemistry in 25% of patients. In HBeAg-negative chronic hepatitis treatment with pegylated interferon for 12 months leads to normal liver biochemistry in 60%, and sustained suppression of hepatitis B virus load below 400 copies/ml in 20% of patients.'

 LAMIVUDINE IN CHRONIC HEPATITIS B INFECTION

'48 weeks of treatment with lamivudine induces anti-HBe seroconversion in 27% of patients with HBeAg-positive chronic hepatitis, despite 38% developing HBV-DNA polymerase mutations. Treatment also improves histology and liver biochemistry.'


ADEFOVIR IN CHRONIC HEPATITIS B INFECTION
'In HBeAg-positive chronic hepatitis treatment with 10 mg of adefovir for 48 weeks produces normal liver biochemistry in 48% (NNTB 3), suppresses serum HBV-DNA in 39% (NNTB 5) and leads to e antigen seroconversion in 14% (NNTB 16) of patients. In HBeAg-negative chronic hepatitis treatment with adefovir for 48 weeks reduces ALT to normal in 72% (NNTB 2.3) and renders serum HBV-DNA undetectable in 55% (NNTB 2) of patients.'


This is a nucleoside analogue which inhibits DNA polymerase and suppresses HBV-DNA levels. It is effective in improving liver function in patients with decompensated cirrhosis and may prevent the need for transplantation. Long-term therapy is complicated by the development of HBV-DNA polymerase mutants which may occur after 9 months of treatment and is characterised by a rise in viral load during treatment. These viral mutants are less hepatotoxic than native virus so the drug can often be continued (Box 23.40). Flares in transaminases occur when lamivudine is stopped if mutant virus is present, as native virus replaces mutant virus.
Adefovir
This is a nucleotide analogue that is phosphorylated to yield active drug which inhibits HBV-DNA polymerase. It reduces HBV-DNA levels by 3-4 logs, enhances the frequency of HBeAg seroconversion and leads to histological improvement, but is contraindicated in renal failure. The HBV-DNA mutants develop at a lower rate than with lamivudine, 2% being identified after 2 years of treatment (Box 23.41). Relapse occurs on stopping treatment and the optimum length of treatment remains unknown. Adefovir is effective in suppressing most of the lamivudine-induced DNA polymerase mutant viruses.
Other drugs
Other drugs which are currently been studied in chronic hepatitis B include tenofovir, which has anti-HIV efficacy, and L-deoxythymidine. The role of combination antiviral therapy, as used in HIV infection, is still unclear.
Liver transplantation
Historically, liver transplantation was contraindicated in the presence of hepatitis B because infection often recurred in the graft. However, the use of post-liver transplant prophylaxis with lamivudine and hepatitis B immunoglobulins has reduced the reinfection rate to 10% and increased 5-year survival to 80%, making transplantation an acceptable treatment option in selected cases.

Prevention



AT-RISK GROUPS MERITING HEPATITIS B VACCINATION IN LOW ENDEMIC AREAS
  • Parenteral drug users
  • Men who have sex with
  • Close contacts of infected individuals
    • Newborn of infected mothers
    • Regular sexual partners
  • Patients on chronic haemodialysis
  • Patients with chronic liver disease men
  • Medical/nursing personnel
Individuals are most infectious when markers of continuing viral replication, such as HBeAg, and high levels of HBV-DNA are present in the blood; they are least infectious when only anti-HBe is present with low levels of virus. HBV-DNA can be found in saliva, urine, semen and vaginal secretions. The virus is about ten times more infectious than hepatitis C, which in turn is about ten times more infectious than HIV.
A recombinant hepatitis B vaccine containing HBsAg is available (Engerix) and is capable of producing active immunisation in 95% of normal individuals. The vaccine gives a high degree of protection and should be offered to those at special risk of infection who are not already immune, as evidenced by anti-HBs in the blood . The vaccine is ineffective in those already infected by HBV. Infection can also be prevented or minimised by the intramuscular injection of hyperimmune serum globulin prepared from blood containing anti-HBs. This should be given within 24 hours, or at most a week, of exposure to infected blood in circumstances likely to cause infection (e.g. needlestick injury, contamination of cuts or mucous membranes). Vaccine can be given together with hyperimmune globulin (active-passive immunisation).
Neonates born to hepatitis B-infected mothers should be immunised at birth and given immunoglobulin. Hepatitis B serology should then be checked at 12 months of age.

Prognosis

Acute hepatitis

Full recovery occurs in 90-95% of adults following acute HBV infection. The remaining 5-10% develop a chronic infection which usually continues for life, although later recovery occasionally occurs. Infection passing from mother to child at birth leads to chronic infection in the child in 90% of cases and recovery is rare. Chronic infection is also common in immunodeficient individuals such as those with Down's syndrome or HIV infection.
Recovery from acute HBV infection occurs within 6 months and is characterised by the appearance of antibody to viral antigens. Persistence of HBeAg beyond this time indicates chronic infection. Combined HBV and HDV infection causes more aggressive disease.
Chronic infection
Most patients with chronic hepatitis B are asymptomatic and develop complications such as cirrhosis and hepatocellular carcinoma only after many years . Cirrhosis develops in 15-20% of patients with chronic HBV over 5-20 years. This proportion is higher in those who are e antigen-positive. 

14 comments:

  1. ALL THANKS TO DR WILLIAMS
    I was diagnosed of hepatitis B in 2011, I have tried all possible means to get cure but all my effort proved abortive, until a friend of mine introduced me to a herbal doctor , who prepare herbal medicine to cure different kind of diseases including hepatitis b virus (HBV), when i contacted this herbal doctor via his email, he sent me hepatitis b herbal medicine via courier service, when i received the herbal medicine he gave me step by step instructions on how to apply it, when i applied it as instructed i was totally cured from this disease within 1 months of usage. any body with similar problem can Contact this great herbal doctor via his email drwilliams098675@gmail.com for advice and for his product,and thanks to you admin for such an informative blog.

    ReplyDelete
  2. I am karen from Canada, I once suffered from a terrible and Chronic hepatitis b,since i was 23 , the doctor told me there was no permanent cure i was given medications to slow down its progress, i constantly felt my health was deteriorating as i constantly had Abdominal pain and vomiting ,this ailment was really terrible especially when am going out with my friends, i have this constant disorder for about 31 years, this was really a terrible ailment ,on thin one day that i was going through the internet,and i came across a post of Mrs kate on how she was been cured from hepatitis b through the help of Dr Williams herbal product, I contacted this herbal doctor via his email and explain everything to him and make purchase of his product,few days later he sent me the herbal medicine through courier service, when i received the herbal medicine, i used it for 1 months as prescribed by dr williams and i was totally cured within those week of usage,on thin now i have not experience any sign or characteristics again . for more information you can email him on drwilliams098675@gmail.com for help

    ReplyDelete
  3. "DR WILLIAMS, I wish to praise you for sharing such a simple but comprehensive herbal medication to tackle this disease from the root. This is truly a valuable resource for all men and woman suffering from hepatitis b. It's been almost 10 years since my doctor first diagnosed me with hepatitis b. My doctor suggested that I will try watchful waiting but as the months went nothing has changed.

    As soon as I decided I'm going all the way and treat my hepatitis b, I ordered Dr Williams and the results as you already know were shocking to say the least. The result I took clearly showed my hepatitis b had completely vanished.

    I have even encouraged my "Doubting Thomas" friend to order it and read it too. To have so much good information in one tight package is an unbelievable value. I would encourage anyone who suffers from hepatitis b or any other disease to take advantage of Dr Williams herbal medicine! you can contact him through his email on drwilliams098675@gmail.com for more information

    Sincerely...

    ReplyDelete
  4. As a sign of gratitude for how my husband was saved from hepatitis b, i decided to reach out to those still suffering from this.
    My husband was diagnosed of hepatitis b in 2013 and it was really tough and heartbreaking for me because he was my all and the symptoms were terrible, he always have Joint pain , and he always complain of Weakness of the body . we tried various therapies prescribed by our neurologist but none could cure him. I searched for a cure and i saw a testimony by someone who was cured and so many other with similar body problem, and he left the contact of the doctor who had the cure to hepatitis b. I never imagined hepatitis b has a natural cure not until i contacted him and he assured me my husband will be fine. I got the herbal medication he recommended and my husband used it and in one months he was fully okay even up till this moment he is so full of life. hepatitis b has a cure and it is a herbal cure contact the doctor for more info on drwilliams098675@gmail.com on how to get the medication. Thanks for reading my testimony.

    ReplyDelete
  5. I am Shelley from Los Angeles,California, I want to testify on how i got cured from hepatitis b, I have suffered from hepatitis b since the year 2011 with so mush pain,that i have to spend so mush money getting pain relief in the hospital, and I have visited several doctor ,but all to no avail, my world was gradually coming to an end because of the pain in my abdomen , until i saw a post in a health forum about a herbal Dr Williams who use herbal portion in curing people from different kind of diseases including hepatitis b, at first i doubted if it we be able to cure me, but i decided to give it a try, when i contacted this herbal doctor via his email, he prepared a herbal portion and sent it to me via courier service, when i received this herbal medicine, he gave me step by step instructions on how to apply it, when i applied it as instructed, i was completely free from hepatitis b just for 1 months of usage,i we recommend this to all my friend family in the world today who still suffering from hepatitis b you can contact him through his email on drwilliams098675@gmail.com for help.

    ReplyDelete
  6. SPECIAL THANKS TO DR WILLIAMS FOR THE HEPATITIS B CURED HE
    RENDER TO ME.
    I'm giving a testimony about Dr. WILLIAMS the great Herbal man, he has
    the herbal cure to hepatitis b, he cured my hepatitis b disease,
    though I went through different website I saw a testimonies about this
    Dr Williams, I was like: 'Dr Williams have the hepatitis b cure why are
    people still suffering from it?' I thought of it, then I contact Dr Williams, I didn't believe him that much, I just wanted to give him a try, he replied my mail and Needed some Information about me, then I sent them to him, he prepared the (CURE) and sent it to me through Courier Service he gave my details to the Courier Office, they told me that 1-3 days I will receive the package and i took the medicine as prescribed by Dr Williams and I went for check-up 1 week after finishing the medicine, then the hepatitis b was not there, if you are suffering from hepatitis b you can also contact him on his via email address: drwilliams098675@gmail.com for his herb

    ReplyDelete
  7. CURE TO HEPATITIS B WITHOUT ANY SIDE EFFECT: My daughter was diagnosed with hepatitis b . My daughter hepatitis b was something i don't understand she cry so bad that she was usually in bed for about 8 hours and soreness killers (even prescription strength) don't stop the crying even if she take triple the dosage. my daughter symptoms was really so terrible,that we have to make hospital our home, and all the doctors would do is monitor it, prescribe him countless of control pills and pain medication with no positive result. until recently I contacted a Doctor who put an end to this problem. If you are having same problem with hepatitis b contact Dr. William for advice and possible solution without any side effect drwilliams098675@gmail.com

    ReplyDelete
  8. With Dr Williams herb i was completely free from hepatitis b.You are an amazing doctor.Matching diagnosises aside, I just want to be your friend. Lol You inspire me on a feminist level. On an intelligence level. you are a good man doing so much for mankind, level.Thank you for being you.For keeping a lot of us . For reminding us that we aren’t a fucking statistic or a status, we are still PEOPLE. With brains and personalities and jobs and lives. I’ve been diagnosed for so many years now with hepatitis b, and the roller coaster of emotions is all too real.I’m sure I speak for everyone here when I say thank you. From the deepest part of my soul. THANK YOU.You give us all an indescribable level of comfort and absurdness in sharing our diagnoses and, almost a green light to continue to celebrate our lives,for you always been there.For every jerk who throws you hate, there are hundreds of us thanking the universe for you.for more information about Dr Williams product to hepatitis b
    you can email him on drwillliams098675@gmail.com

    ReplyDelete
  9. Thanks to Dr Williams I am so happy today, I have been suffering from hepatitis b for the past 8 years now, and i have spent a lot on western drugs which has all proved abortive, i have tried all means in life to become hepatitis b free , but there was no answer until i decided to try herbal solution and i found Dr Williams online and i contacted him and after I took his medication as instructed, i am now completely free from hepatitis b within those week of usage, i am so much happy, thanks to Dr Williams for helping me get my life back again without any form of crisis, i promise to tell your name and good deeds to the whole world,if you have hepatitis b you can email him on drwilliams098675@gmail.com for more information .

    ReplyDelete
  10. I am Shelley from Los Angeles,California, I want to testify on how i got cured from hepatitis b, I have suffered from hepatitis b since the year 2011 with so mush pain,that i have to spend so mush money getting pain relief in the hospital, and I have visited several doctor ,but all to no avail, my world was gradually coming to an end because of the pain in my abdomen , until i saw a post in a health forum about a herbal Dr Williams who use herbal portion in curing people from different kind of diseases including hepatitis b, at first i doubted if it we be able to cure me, but i decided to give it a try, when i contacted this herbal doctor via his email, he prepared a herbal portion and sent it to me via courier service, when i received this herbal medicine, he gave me step by step instructions on how to apply it, when i applied it as instructed, i was completely free from hepatitis b just for 1 months of usage,i we recommend this to all my friend family in the world today who still suffering from hepatitis b you can contact him through his email on drwilliams098675@gmail.com for help.

    ReplyDelete
  11. God bless Dr.Ebhos for his marvelous
    work in my life, I was diagnosed of Hepatitis B.
    since 2011 and I was taking my medications, I
    wasn't satisfied i needed to get the Hepatitis B,
    out of my system, I searched about some possible
    cure for Hepatitis B. i saw a comment about
    dr.Ebhos . He was from West Africa ,
    how he cured Hepatitis B, with his herbal
    medicine, I contacted him and he guided me. I
    asked for solutions, he started the remedy for my
    health, he sent me the medicine through (UPS)
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    ONCE AGAIN THANK YOU SIR
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    11 Hepatitis B and many more........ he will send
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    ReplyDelete
  12. My testimonies about the great herbal man that cured me from hepatitis B, his name is Dr ebhota. i was diagnose of hepatitis b 4 years ago, i almost spent all i had then, until i saw Dr Ebhota recommendation online, and i call him, them he told me how to get the herb.with in one month of using the herb i got my complete cure from hepatitis b,Dr Ebhota i pray that God we give you more life to live on earth to enable any one who need your herb to also benefit from it,you can contact him on +2349035324155 or email him drebhota123456@gmail.com

    ReplyDelete
  13. end Or Understand What Was Going On With Me But I Had A Believe In My Faith And Keep Hoping For a Better Solution . I Went To Several Hospitals Seeking Medication And Help But All Turned Out To Say The Same Outcome That There is " No Cure ". One day I Was Searching Online Magazines For My Cousins Wedding Gown, As I Came Across A Page Of Testimonies And Articles About A Herbal Medication For Hepatitis B Virus And Testimonies On How The Medication Has Help Out a lot Of People .

    Immediately I Email The Clinic Or The Hospital Called " Medication Clinic " , And Immediately I Was Attended To You , I Immediately Order My Own Package Of My Herbal Prescribed Medication Which Only Took About 2Days To Be Delivered to My House Address. At First When I Received My Herbal Medication I Was Scarred To Drink It But My Life Depended On It So I Had No Choice I Had To Save My Life . Right Now Im Super Excited To Say , This Is Making It The 5th Month After Drinking The Medication . Now I Am Fine, I Don't Suffer From Any Pains And Headaches Anymore . I Recently Went To See My Doctor About My Health Status I Was Told I'm totally fine , and that the blood Clotting, Blood Pressure, My Immune System And My Health Are All Fine . All Thanks To Doctor Carly and the Medication Clinic In General .

    If There Is Anyone Passing Through This Kind Of Life dreading Disease Or Circumstance , Please Hurry Up To Medication Clinic For Better Treatment And Inquiries .

    Here Is The Contact Details MedicationClinic@Gmail.Com

    ReplyDelete
  14. I was diagnosed as HEPATITIS B carrier in 2013 with fibrosis of the
    liver already present. I started on antiviral medications which
    reduced the viral load initially. After a couple of years the virus
    became resistant. I started on HEPATITIS B Herbal treatment from
    ULTIMATE LIFE CLINIC (www.ultimatelifeclinic.com) in March, 2020. Their
    treatment totally reversed the virus. I did another blood test after
    the 6 months long treatment and tested negative to the virus. Amazing
    treatment! This treatment is a breakthrough for all HBV carriers.

    ReplyDelete