Path: Liver 3 - Acute + Chronic Hepatitis (ii)
HAV
faceal-oral spread with enteral transmission
personal/sexual contact
epidemic (esp in institutions)
contaminated water/shellfish
most cases typically have +ve travel hx to endemic areas (South Asia + Africa)
usually subclinical/mild illness
silent in children (reservoir)
more often symptomatic (jaundice+fever) in adults
v rare cause of ALF
jaundice can be prolonged
no chronic disease/carrier state
anti-HAV Ab gives lifelong immunity
IgM anti-HAV indicates acute infection (4-8wks), then IgG becomes +ve
can be induced by active vaccination
elevated ALT 1 month after exposure (comes down @ 2 months)
HEV
similar illness + epidemiology to HAV
mainly in developing countries - water borne outbreaks
genotype 1 = commonest cause of ALF in S Asia
genotype 3 = zoonotic, causes sporadic cases in non-endemic countries
serological + molecular tests now available
mostly subclinical/mild, rarely ALF
higher risk of more serious disease in pregnant women - unsure why
in general no chronic disease/carrier state
chronic disease described in immunosuppression
HDV
delta agent
passenger RNA virus: requires presence of HBV for rep
either co-infection with HBV or superinfection on background of existing chronic HBV
increases risk of chronic disease a/w HBV
typically in IVDUs
rare in Ire
HCV
major cause of blood/blood product associated hep
major burden of chronic infection worldwide - prevalence varies widely
6 genotypes (determine behaviour, tx response)
transmission
blood
IVDUs
sporadic
sometimes sex
pathogenesis uncertain
acute infection typically silent, seldom recognised
most cases (>80%) progress to chronic
chronic infection often identified incidentally
chronic HCV a/w vague symptoms - fatigue, arthralgia
small % develop extra-hepatic manifestations
Anti-HCV Ab simply indicates exposure
most have active chronic infection (viraemia)
not protective
HCV RNA in blood confirms ongoing infection - find amount + genotype
type 1a: commonest in US, least responsive to IFN
type 1b commonest in Europe
type 2+3 elsewhere
tx
polymorphism in human IFNL3 aka IL28B gene predicts response to tx in type 1
sustained virological response (SVR) = nil/minimal RNA after 12-24wks, reduces progression to cirrhosis + HCC
risk of progression to chronic varies
increased risk in men, over 50s, coexisting HIV/HBV, alcohol, obesity
progression may take 20-30 yrs
20% will have cirrhosis over 20yrs
histology
indicates damage
requires biopsy
predicts risk of progression
now there are non-invasive assessments of fibrosis (FibroScan)
biochemistry may be normal, clinically may be silent
pegylated IFN alpha + ribavirin
used to be 1st line
SVR in 50%
best response rate in genotype 2+3
biopsy genotype 1 to assess suitability for tx
long duration, injection, SEs, exclusions
DAAs
rapid development of agents
oral
few SEs
can be used in combo
expensive
aim: IFN free regimens
high % SVR, esp genotype 1
effective in previous non-responders, those who relapsed after tx, cirrhosis, HIV co-infection, post-transplantation