17. Chronic hepatitis B Flashcards
what are the hep b modes of tram is soon
placental to fetal - risk of it being chronic is high if infected from neonate
HBsAG positive mothers
with high HBV DNA
tenofovir needed
blood exchange - high hbv DNA
sexual transmission - through semen and fluids
there is HBV found in
urine , feces , sweat , tears , breast milk = however low HBV and no evidence that it can transmit
prevented by HBV vaccination alone
describe HBV structure ?
nucleocapsid
partially double stranded circular DNA with dna polymerase and reverse transcriptase = for replication
=HBcAG
between two - HBeAg
outer envelope of surface protein = HBs antigen
HBV pathogenesis ?
viral genomic DNA transferred to the cell nucleus by host proteins called chaperones.
The partially double-stranded viral DNA is then made fully double stranded by a viral polymerase and transformed into covalently closed circular DNA (cccDNA)/ episcopal viral DNA
= stable form of hBV DNA
SOURCE FOR REPLICATIONS and REACTIVATION AFTER IMMUNOSUPPRESION
This cccDNA serves as a template for transcription for viral mRNAs by HOST RNA polymerase.
part of hbv integrates into host genome - integrated viral dna - causation of HCC
how many genotypes of HBV is there ? and describe their geographic distribution
8 -A B C D E F G H
A, D = europe and USA
D = balkan peninsula and mediterranean 100 percent of bulgarian HBVD
D highly susceptible for development of mutations in “pre-core” region
giving Prevalence of HBeAg negative chronic hepatitis
Associated with poor results of interferon treatment
B, C = asia
which genotype respond well to interferon therapy ?
genotype A
HBsAg mutants lead to ?
changes in the antibody binding domain and the usual tests for HBsAg may (-)
Mutation in the pre-core region leads to ?
creates a stop codon prevents the production of HBeAg, but the synthesis of HBcAg is unaffected -> pattern of HBeAg (-) hepatitis
DNA polymerase mutants leads to ?
after lamivudine therapy -> genetic resistance to drugs
describe the hep Viral markers to diagnostics
alt i usually higher
acute
first antibody IgM anti HBc
HBcAG
which disappear in weeks
also HBs antigen which does not disappear
IgG antiHBc detected = maybe present for life (post exposure)
HBe antigen = acute
persistence implies of HBe antigen- continuous infectious state
and chronicity
and severity
low high hbv dna in blood
= implies viral rep
————-
if vaccinated only anti HBs antibody
no hbv dna in blood
if chronic
IgG antiHBc
HBs antigen
with or without HBe antigen
anti HBe
low high HBV dna in blood
= implies viral rep
————-
if cleared hep b
IgG antiHBc = best marker for past exposure to infection
anti HBs
with or without anti HBe
no HBV dna in blood
a person can have HBV infection but no hepatitis how is that ?
HBV infection = minimal replication
no / mild liver inflammation
hepatitis b = active replication and liver inflammation and fibrosis progress
what are the phases of chronic HBV infection
phase 1 - HBe antigen positive chronic INFECTION
high HBV DNA - HIGHLY REPLICATIVE ( above 20,000iu/ml)
normal or low ALT
high HBs antigen
mild or no necroinflamfmation
phase 2 - HBe antigen positive chronic hepatitis
IMMUNE IS ACTIVE
declining HBV DNA
fluctuating but high ALT
DECLING hbs antigen and HBE - antigen
acute or intermittent hepatitis
EMERGENCE OF CORE AND PRECORE MUTATIONS
phase 3 - HBe antigen negative chronic infection
(inactive / carrier)
undetectable HBV DNA (below 2000 IU/ml)
ALT return to normal
low HBS antigen - but still positive
anti HBE positive
progressing inflammation and fibrosis
phase 4 - HBe antigen negative chronic hepatitis
(REACTIVATION - by corticosteroids - RITUXIMAB)
elevation of HBV DNA (above 2000 IU /ml)
fluctuating but high ALT
low HBS antigen - but still positive
anti HBe
GREATEST RISK FOR CIRRHOSISI AND HCC
phase 5
OCCULT HEP INFECTION - RESOLVED
HBS antigen FINALLY negative
HBV DNA returning to normal in serum but still present in liver
ALT return normal
ask of reactivation with immunosiuppresions
Spontaneous HBeAg seroconversion is associated with ?
prolonged remission
Spontaneous HBsAg seroconversion is associated with
cure
what are the indication for treatment of chronic hepatitis b ?
ALT elevation more than 1.5 ULN
HBV DNA more than 2000 IU/ml
in cirrhotic patient ever detected HBV DNA is very important
cytology stats of fibrosis
pregnant mothers with high HBV DNA
what is the aim of therapy in HBE antigen negative chronic HEPATITIS
HBs antigen clearnace
sustained immune control achieved with PEGLYATED interferon alpha therapy
HBV DNA suppression
life long maintenance suppression of HBV DNA =
NUCLEO ANALOGUES-prevent reactivation in patients who are inactive aswell
