Case 15: Jaundice (My liver tests are abnormal) Flashcards
which types of hepatitis are transmitted via faecal oral route
A and E
which types of hepatitis are transmitted via blood and bodily fluids route
B, C,D
what types of hepatitis are acute
A
what types of hepatitis are acute and chronic
B,C,D
what types of hepatitis are chronic
E
what is hepatitis D associated with
only people with hepatitis B can be infected with hepatitis D
what is hepatitis E associated with
it is rare and associated with immunosuppression
what are the 4 essential functions of the liver
produces clothing factors for clotting cascade
stores excess glucose as glycogen
stores/detoxifies harmful endogenous and exogenous substances (cellular debris, bacteria, drugs)
metabolism of carbohydrates, fats and proteins
3 most common causes of liver cirrhosis in the western world
non-alcoholic fatty liver disease
alcohol-related liver disease
chronic viral hepatitis
hepatitis B serology interpretation
Hepatitis B core antibody IgM (anti-HBc IgM) - appears within weeks of acute infection and remains detectable for 4-8 months
Hepatitis B core antibody IgG (anti-HBc IgG) - detectable in virtually all patients exposed to hepatitis B. Can be positive in both acute and chronic infection
Hepatitis B surface antigen (HBsAg) - first serological marker to become positive in a new, acute Hepatitis B infection. Detected on average 4 weeks after exposure to the virus. Usually becomes undetectable after 4-6 months. Detection after 6 months implies chronic hepatitis B infection
Hepatitis B surface antibody (HBsAb or Anti-HBs) - detected in the blood after person is able to clear Hepatitis B surface antigen. The presence of Hepatitis B surface antibody following acute infection suggests complete resolution of infection. It is also detectable in those immunised against hepatitis B
Hepatitis B e-antigen (HBeAg) - present in new acute infection and associated with high Hepatitis B virus DNA levels (HBV DNA)
Hepatitis B DNA - patients with high Hepatitis B DNA levels are more infectious
questions to ask about an overdose
number of tablets taken and the dose
was it taken once or staggered over time
timing- delay presentation may indicate a greater degree of liver toxicity
any other medication/drugs taken alongside
any medical conditions (including history of alcohol abuse)
what regular medications do they take (over counter, prescribed and herbal)- these may increase hepatotoxicity
what features may make you think a person is at serous risk of self harm
background of mental health problems
was the overdose planned- suicide note, changes to will, measures in place to prevent rescue
triggers- physical health problems, unemployment, bereavement, changes in relationship, social isolation, domestic violence
young/middle-aged men are at higher risk
how did they present to social services- was it them/someone else found them
how do they feel now- do they regret it/wish it was successful
what features on examination may indicate hepatotoxicity
confusion due to hepatic encephalopathy
liver asterixis (flapping tremor)
jaundice- skin/sclera
bruising of skin/bleeding gums/bleeding from anywhere- due to clotting derangement
tenderness in RUQ- liver inflammation
hepatomegaly
which herbal medication can increase risk of liver toxicity
St. Johns wart
what is a drug which can cause liver fibrosis
methotrexate
what are ALT and AST
they are enzymes found in hepatocytes which leak out and are found in large amounts when there is significant hepatic parenchymal damage
aside from liver injury, what may also increase ALT and AST levels
MI (they are found in the heart too)
rnhabdomylosis (they are found in skeletal muscle too)
haemolysis (they are found in RBCs too)
where is ALP found
liver, bone and placenta
what can increased ALP indicate
biliary obstruction
boney disease (Padgets)
fractures
metastatic disease
osteoperosis and myeloma typically don’t raise ALP unless associated with fractures
how to distinguish whether raise in ALP is due to liver or boney disease
look at GGT as well (it is raised in liver disease but not in boney)
what stages in life causes ALP to rise
during periods of growth (adolescence and pregnancy)
where is GGT found
liver
renal tubules
pancreas
intestine
aside from liver disease what can cause a raise in GGT
enzyme induction- for example prolonged exposure to hazardous alcohol and to some drugs (rifampicin, phenobarbitone, griseofulvin)
what is albumin and where is it made
is the predominant blood protein and is largely made by the liver
why might albumin levels be low
poor underlying liver systemic function
any illness can cause decreased albumin
extreme malnutrition
nephrotic syndrome (losing protein from kidneys)
protein losing enteropathy (losing protein from the intestines)
what is bilirubin
a waste product produced by the catabolism of haemoglobin
the liver and bilirubin
the liver is involved in the breakdown of Hb and conjugating bilirubin to make it water soluble for the its excretion in bile
what may cause raised bilirubin
pre-hepatic jaundice (increased red cell breakdown)
hepatic jaundice (reduced liver function)
post-hepatic jaundice biliary obstruction
what is Gilberts syndrome
there is low levels of conjugating enzymes which causes raised levels of unconjugated bilirubin in the presence of otherwise normal LFTs
what % of the population have Gilberts syndrome
5%
what markers are used to monitor chronic liver disease
serial measurement of albumin and bilirubin over long periods of time
those with chronic liver disease (cirrhosis) may have completely normal or only slightly raised LFTs
what is the most common cause of hepatic failure in the UK
paracetamol overdose
initial non-specific symptoms of paracetamol overdose
nausea/vomiting
abdominal pain
signs and symptoms of paracetamol overdose to be concerned about
acute confusion (encephalopathy)
reduced urine output
hypoglycaemia
reduced GCS
what treatment is given in paracetamol overdose
N-acetylcysteine (works as a glutathione donor, preventing the toxic build-up of NAQPI)
when should you commence acetylcysteine treatment
those with a high plasma-paracetamol concentration (on graph)
those presenting within 8-24hrs after ingesting more than 150mg/kg of paracetamol regardless of plasma-paracetamol concentration
those who present after 24hrs in they are- jaundiced, hepatic tenderness, elevated ALT above their normal, INR greater than 1.3 or paracetamol concentration is detectable
possibly give if they present within 24hrs with normal plasma-paracetamol, but have acute liver injury on biochemical testing
what dosage of paracetamol indicates high toxicity risk
above 150mg/kg in 24hr period
when should you be admitted to hospital for paracetamol overdose
if symptomatic
ingested more than licensed dose and more than or equal to 75mg/kg in any 24hr period
ingested more than the licensed dose but less than 75mg/kg per 24hrs on each of the preceding 2 or more days
what is a staggered overdose
ingestion of potentially toxic dose of paracetamol over more than one hour with the possible potential of wanting to cause self harm
management of staggered overdose
hospital admission
treated with acetlycystiene without delay
if you are unsure about a patients risk of liver toxicity following paracetamol overdose, where should you get advice
national poisons information service
what are the indications for liver transplant following paracetamol induced acute liver failure
arterial pH less than 7.3 or arterial lactate over 3 after adequate fluid resuscitation or if the 3 below happen within a 24hr period
creatinine over 300micromol/L
PT over 100 seconds (INR over 6.5)
grade III/IV encephalopathy
what is the most common reason for liver transplant and acute liver injury in UK
paracetamol overdose
when does toxicity peak after paracetamol overdose ingestion
48-72hrs after ingestion
liver toxicity is increased in people with what physiology
toxicity is from paracetamol metabolites therefore it is increased in people who have more highly induced cytochrome P450 physiology
what can be seen on ABGs in acute liver failure
acidosis
what is the best early indication of severity of liver failure
prothrombin
what type of glucose concentration can be seen in hepatic necrosis
hypoglycaemia
when should paracetamol levels be taken
4 hrs post ingestion
ASAP if staggered
ASAP if dose was more than 4 hrs ago
definition of acute liver failure
liver failure with the presence of hepatic encephalopathy in a patient without pre-existing liver disease
management of acute liver injury with coagulopathy
catheterisation and hourly monitoring of urine output
hourly capillary blood glucose recordings
10mg of vitamin K IV
repeat coagulation panel in 6 hrs
what clinical signs would you look for as an indication the patient is developing liver failure
spontaneous bruising/bleeding at venipuncture sights (coagulopathy sign)
reduced urine output (AKI)
hypoglycaemia (hepatic necrosis)
metabolic acidosis despite hydration
hypotension despite hydration
encephalopathy (agitation, confusion and aggression rather than drowsiness seen in chronic liver disease)
other causes of acute liver failure
severe acute viral hepatitis (especially E in pregnancy but also A and B)
acute vascular injury to liver (Budd Chiari syndrome)
autoimmune hepatitis
direct exposure to toxins (amanita mushroom poisoning)
mental health management of overdose patients upon discharge
mental health liaison service for review
follow-up by mental health home treatment team in the community
GP follow-up on discharge
what may cause raised ALT (with otherwise normal LFTs)
indicates liver inflammation (hepatitis), this could be due to:
fatty liver related to alcohol
viral infection
non-alcoholic related fatty liver disease
autoimmune disease
rarer-
alpha1 antitrypsin deficiency
Wilsons (presents at younger age)
what blood transfusions may increase your hepatitis risk
those before 1991
what may a mild raised MCV suggest
liver cirrhosis
what may a largely raised MCV suggest (over 110fl)
hazardous alcohol consumption
what antibodies to look for in autoimmune liver disease
antinuclear
anti smooth muscle
antimitochondrial
what timeframe is considered chronic hepatitis
over 6 months
what is cirrhosis
prolonged fibrosis and scarring of the liver
there must be nodules for it to be cirrhosis
what other viruses can cause hepatitis
herpes (EBV epstein barr, HSV, CMV)
adenoviruses
coronaviruses
what can the 3 results of acute hepatitis be
- recovery
- chronic hepatitis (over 6 months)- there is inflammation, increasing fibrosis and then cirrhosis
- fulminant hepatitis- requires transplant and can cause death
acute hepatitis symptoms
generally unwell
jaundice
RUQ ache
stool/urine discolouration
if severe- confusion/drowsiness, hypoglycaemia, coagulopathy
blood results in acute hepatitis
raised ALT/AST- over 1000
raised bilirubin
if severe- acidosis, increased lactate, coagulopathy, renal impairment
chronic hepatitis symptoms
often none
fatigue
typically presents with cirrhosis
bloods with chronic hepatitis
abnormal LFTs (mild elevation in ALT)
what is fulminant hepatitis
acute hepatitis with liver failure
there is encephalopathy within 28 days of jaundice (in those without pre-existing liver disease)
abnormal results in fulminant hepatitis
acidosis
coagulopathy
hypoglycaemia
what can cirrhosis cause
loss of function:
jaundice
coagulopathy
decreased drug metabolism
decreased hormone metabolism
increased sepsis
portal hypertension:
varices
piles
ascites
encephalopathy
renal failure
what is the transmission of hep A associated with
poor sanitation
food preparation
travel
is an endemic for children in low income countries
is there a vaccine for hep A
yes (active and passive)
those with cirrhosis should be vaccinated
99% if people with hep A what
recover (it is acute)
clinical presentation of hep A
jaundice within 2 weeks
when are you infectious with hep A
week 1-5
in hep A and E what do IgM and IgG mean
IgM= acute infection
IgG= immune
treatment of hep A
supportive as they will get better on their own after a few weeks
what is hep E transmission associated with
poor sanitation
food preparation (pork)
travel
childhood endemic in south asia and north africa
is there a vaccine for hep E
no
hepatitis E can develop into chronic in which group of people
immunosupressed
hepatitis E can develop into fulminant in which group of people
in pregnant women in 2nd/3rd trimester
treatment of hep E
supportive
if chronic- reduce immunosuppression, ribavirin
what group of people mainly get hepatitis C in UK
intravenous drug users
what group of people mainly get hepatitis C in the rest of the world
medially due to poorly sanitised equipment
is there a vaccine for hep C
no
is sexual transmission common for hep C
no it is rare (more common in men who have sex with men however)
do the majority with hep C have an acute or chronic infection
80% go on to develop chronic
does hepatitis C cause symptoms
rarely
who is screened for hep C
donors
IVDUs
those with abnormal LFTs
testing for hep C
antibodies
PCR (genotype and viral load)
treatment of hep C
direct acting antivirals (DAAs)
how are DAAs used for hep C
used for 8-12 wks
advantages of DAAs
side effect free
over 95% cure rate
disadvantages of DAAs
they are expensive however
reinfection may occur
which is the only hepatitis virus which is DNA
hep B
most common transmission of hep B worldwide
vertical (from mother to child)
after tobacco what is the worlds second biggest carcinogen
hep B (meaning it causes cancer)
is there a vaccine for hep B
yes using surface ag
are the majority of hep B infections chronic or acute
in adults, majority acute
in babies, majority chronic
what is used to determine the progression of fibrosis in the liver
elastography
when are people with hep B infectious
at 12-28 wks
treatment of hep B
acute:
usually not necessary
nucleoside analogues if severe
chronic:
nucleoside analogues
interferon
what does hepatitis delta need from hep B
needs its surface ag
what does hep delta do to hep B prognosis
it worsens it
treatment for hep delta
interferon (1-2 years and may have limited effectiveness)
what % of population have non-alcoholic fatty liver disease
20%
what % of those with diabetes have non-alcoholic fatty liver disease
70%
stages of non-alcoholic fatty liver disease
first is hepatitis steatosis (fat content over 5% of liver volume)
progresses to non-alcoholic fatty liver disease when inflammation begins
patients with non-alcoholic fatty liver disease are at a higher risk of what
progression to fibrosis, cirrhosis and hepatocellular carcinoma
lifestyle advice for non-alcoholic fatty liver disease
weight loss
reduce alcohol intake
Wilsons disease and liver
hepatic involvement typically presents with chronic hepatitis, cirrhosis or acute liver failure
other symptoms of Wilsons
tremor
behavioural problems
depression
what indicates Wilsons
low serum caeruboplasmin
treatment of Wilsons
copper chelation agents
lifestyle advice for hep C
vertical and sexual risk (don’t need to encourage condom use but possibly with men who have sex with men) is low but partners and children can be screened is they wish-
avoid blood borne contact (toothbrushes and razors)
reduce alcohol intake to reduce risk of fibrosis
doesn’t need to disclose the infection to anyone
screening those with hep C
ultrasound screening for detection of hepatoma
offer endoscopic screening for varices
complications of hep C
liver cirrhosis
skin complications (prophyria cutanea tarda)
sjogrens syndrome
hepatocellular carcinoma
