What are the symptoms of viral hepatitis B during acute disease?
Fever, rash, arthritis
MALAISE, ANOREXIA, nausea, RUQ pain, DARK URINE, JAUNDICE
During acute state, high IgM anti-HBcore
How can we tell when a person is infectious with HBV?
Acutely infected vs chronically infected with HBV?
During acute viremia, HbeAg
(antigen against envelope)
Chronic infection is > 6months
Labs: HBsAg, HBeAg, ANTI-HBc
you will NOT SEE: anti-HBsAg or anti-HBcAg
What is the average incubaiton period of HBV?
what percent of pt with HBV proceed to chronic hep?
What are the long term effects?
avg 3 months
3-10% --> chronic hep
Casual association with HCC
What type of virus is HBV?
What is unique about its replication?
hepadnavirus, enveloped, partial DS circular DNA virus
Replication involves a circular RNA genome intermediate
Virus encodes and carries a reverse transcriptase
Virus encodes several proteins (HBsAg; HBe/HBc) that share genetic sequences but with different mRNAs or in-frame start codons (AUGs)
Hepadnavirus replication is unique in that it involves reverse transcription of a RNA into DNA and the partially double-strand DNA is the genetic information found in the virus particles.
HBV infected cells produce and release large amounts of HBsAg particles lacking DNA
The HBV genome can integrate into the host chromosome
How does HBV replicate?
Following entry into the hepatocyte and uncoating of the nucleocapsid core, the partially double-stranded DNA genome is completed by enzymes in the core an then delivered to the nucleus.
Transcription of the genome produces four mRNA including a mRNA larger than the genome (3500 bases).
The mRNA moves to the cytoplasm and is translated into protein. Core proteins assemble around the 3500 base mRNA and (-) sense DNA is synthesized from the mRNA template by the viral polymerase (reverse transcription). This step is sensitive to lamivudine. The polymerase then uses the (-) sense DNA as a template for the synthesis of the partial by a completion of the (+) DNA. Virus particles are then released by exocytosis.
What determines how HBV will present in an individual?
individuals immune response to the infection
How can we best make the diagnosis of HBV active infection?
How can diagnose a past infection?
IgM antibody to hepatitis B core antigen in serum
[anti HBC IgM positive]
In pt with self-limiting anicteric disease, HBsAg detection is serum may also occur
Past infection with Hepatitis B is best determined by detecting anti-HBc, anti-HBs or both.
Chronic infection with Hepatitis B is best detected by persistence of HBsAg in blood for more than 6 to 12 months
What therapy is available for HBV?
Lamivudine, a nucleoside analogue, was approved by the FDA for use in combination therapy against HIV
Hepsera is an acyclic nucleotide analogue of adenosine monophosphate. It inhibits HBV RT by competing with the natural substrate deoxyadenosine triphosphate and by causing DNA chain termination after it’s corporation
In addition, entecavir (2005), telbivudine (2006) and tenofovir DF (2008) (all RT inhibitors originally developed for HIV) have been shown to be effective for inhibition of HBV.
Is there any prophylaxis we could against HBV?
HBV vaccine is safe and effective
HBsAg manufactured by yeast via recombinant DNA technology
Active immunization with recombinant HBsAg vaccine is recommended for healthcare workers and has been incorporated into childhood vaccine schedule
How can a person acquire HDV?
What are the consequences of HDV infection?
Genome- circular RNA
HDV is transmitted via blood, either as a co-infection with HBV or, a HBV carrier can be superinfected with HDV (although the contaminated blood probably also contains HBV).
HDV infection results in fulminant hepatitis with a high mortality rate (mortality rate varies depending on the study but estimates are 40-60% mortality).
If the patient survives, they can also be persistently infected with HDV.
What type of virus is HDV?
How does it replicate?
What is unique about its replication mxn?
35 nm particle-HBsAg on the surface
Capsid- delta antigen (the only protein encoded by the virus)
Genome- circular RNA
The single-stranded, circular RNA is thought to replicate via a "rolling circle" mechanism:
The delta virus RNA acts as a ribozyme to cleave itself.
The linear RNA then ligates itself back together into a circle. This self-cleavage, selfligation property is very unique, only HDV RNA and some plant viroid RNAs have this ability
How can we diagnose a HDV infection?
Diagnosis is made most commonly by detecting IgM or IgG to delta antigen in serum.
IgM antibodies appear within 3 weeks of infection and persist for several weeks.
IgG antibodies persist for years.
What occurs during the HBV window period?
During the window period, antigen might be gone and antibodies to surface antigen might not be detected
Antigen and antibody both could be negative
What geographical areas have high incidence of HBV?
Africa and south east asia
How is HCV detected?
Infection with HCV is generally detected by demonstration of anti-HCV antibodies. Unfortunately, the antibody responses in acute disease may remain negative for 1 to 3 weeks after clinical onset.
Reverse-transcription-polymerase chain reaction (RT-PCR) assay can also be performed to detect HCV RNA in the sera.
Antibody assays are most helpful in chronic hepatitis, especially when multiple antigens are sought.
what are the new antiviral agents available to combat HCV?
use of DAAs leads to a sustained virologic response/cure!
Protease Inhibitors (NS3)
Phosphoprotein inhibitors (NS5A)
Polymerase Inhibitors (NS5B)
Multiple drug regimen most effective
three main targets of drugs - 2 could now be used at the same time
what type of infection?
what is its major consequence?
Is there anything we can do to protect ourselves?
Hep E is a positive strand RNA virus, rarely seen in the USA, mostly in SE Asia (India, Nepal)
Causes acute viral infection
HIGH MORTALITY IN PREGNANT WOMEN
Vaccine: Killed virus vaccine elicits protective immunity but not yet FDA approved