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Path: Liver 4 - Disease + Cirrhosis (i) (Alcoholic hepatitis (classic…
Path: Liver 4 - Disease + Cirrhosis (i)
Fatty change
aka steatosis
abnormal retention of lipids within a cell or organ
macro vs micro vesicular
depends on size + no. of droplets with hepatocyte cytoplasm
macro = common/typical type (most cases), single large droplet of TG in many hepatocytes
unless specifically qualified it is macro
micro v rare
a/w ALF
reflects profound metabolic upset in hepatocyte mitochondria
acute fatty liver of pregnancy
tetracycline toxicity
often only seen on post-mortem
toxic accumulation of multiple tiny droplets of reactive FAs
fat droplets highlighted by staining red with Oil Red O stain
fat lobules dissolve on slides - leave holes
reversible cellular change
metabolic response
a/w alcohol, metabolic syndrome (conditions a/w age + weight that increase CV risk: insulin-resistant type 2 DM, hyperlipidaemia, low HDL chol, obesity, HTN)
other causes: starvation, bariatric surgery, TPN (ICU), amiodarone
Fatty liver disease
spectrum...
Fatty change
commonest manifestation by far
only significance = marker of predisposition
Dx
US (@ least 30% replacement by fat needs to have occurred for it to be visible)
LFTs (transaminases) may be mildly abnormal
CT
steatohepatitis
fatty change a/w inflamm
potential to progress to advanced fibrosis
distinctive histology
characteristic pattern of inflamm/necrosis/fibrosis
lobular (not portal) inflamm/necrosis, centred in vicinity of hepatic vein branch (zone 3)
neutrophils in inflamm infiltrate
Mallory's hyaline within hepatocytes
dense pink intracytoplasmic inclusions
altered intracellular proteins
marker of cell injury typical for alcohol-related damage but not specific
perivenular fibrosis (around small central hep vein branches)
common causes: alcoholic steatohepatitis, non-alcoholic steatohepatitis (NASH)
cirrhosis
Alcohol + the liver
broad correlation: duration/amount of alcohol + risk of significant alcohol-related liver damage
only 30% of those with harmful/risky alcohol consumption/dependency develop alcohol-related liver damage, 10-15% develop cirrhosis
hence host factor important
F>M
others not well-defined
possibly nutrition, drinking patterns, type of alcohol drank
"J-shaped curve" of all-cause mortality in relation to alcohol intake
+ve benefit comparing low intake to none? old wives tale?
heavily criticised - non-drinker pop incl ex-drinkers, only western pop
evidence supporting low alcohol consumption reduces risk of ischaemic stroke + CAD
fatty liver progression -> alcohol hep -> cirrhosis
Units of alcohol
1 unit = 10ml (8g) of pure alcohol
750ml bottle of wine @ 13% = 9.5 units
how big is your glass of wine?
175ml glass = 2.3 units
1 pint of Guinness @ 4.2% = 2.4 units
UK guidelines
men: no more than 3-4/day, not >21/wk
women: no more than 2-3/day, not >14/wk
safe upper limits
if all units consumed, should be spread over @ least 3 days
avoid alcohol if pregnant or planning to be
Alcohol metabolism
oxidative pathway to acetaldehyde + then acetate
secondary MEOS pathway subsidiary, usually minor role, induced in heavy drinkers - produces more reactive/toxic intermediates
pathogenesis of liver injury
altered intracellular metabolism
fat synthesis stim, FA oxidation inhibited
free radicals generated via MEOS pathway
acetaldehyde toxic
modified proteins antigenic
Alcoholic hepatitis
alcohol triggers liver inflamm - unsure why
classic clinical syndrome
malaise
jaundice
low fever
hepatomegaly
raised WCC
if severe may have features of decompensated liver disease (ascites, HE, high INR)
AST:ALT ratio > 2
some have underlying cirrhosis
mortality = 40% @ 6 months if severe
abstinence essential but does not guarantee survival
give steroids if severe
assessment
NB alcohol related cirrhosis often NOT preceded by clinical episodes of alcoholic hepatitis
alcohol related steatohepatitis may be silently progressive