liver Flashcards
symptoms of liver disease
Numerous symptoms Jaundice Ascites Puritis Changes in faeces/urine colour Fat in Faeces Blood clotting irregularities Cutaneous signs
tests for liver disease
Liver Function Tests (LFTs) indicate liver disease
Generally blood tests
Mainly liver enzymes and proteins
Normal ranges vary
possible to have “abnormal” results and functional liver
Important that full medical history also assessed
Some medications alter values of tests
Some medical conditions affect tests
what can be defined as acute liver disease
Acute Self limiting episode History of disease <6 months e.g Paracetamol overdose Viral infections
what can be defined as chronic liver disease?
Chronic
Long term damage to liver
>6 month history
Potential for permanent structural changes
Alcoholic cirrhosis
Non-alcoholic fatty liver disease (NAFLD)
Non-alcoholic steatohepatitis (NASH)
Viral infection
Hereditary conditions
liver disease can also be classed as damage types:
Cholestatic –
bile flow is reduced or blocked/impaired
Elevated ALP, GGT, bilirubin, bile acids and cholesterol
Hepatocellular –
damage to hepatocytes
ALT and AST release by damaged cells
Serum levels may be elevated
Both types of damage can lead to Fibrosis
chronic liver disease progression
- normal liver inflammatory damage, matrix deposition, parenchymal death, angiogenesis (formation of new blood vessels) -early fibrosis disrupted architecture, loss of function -cirrhosis liver failure -hepatocellular carcinoma or liver transplant
chronic liver disease progression
- normal liver inflammatory damage, matrix deposition, parenchymal death, angiogenesis (formation of new blood vessels) -early fibrosis disrupted architecture, loss of function -cirrhosis liver failure -hepatocellular carcinoma or liver transplant
what are complications with severe liver disease?
Symptoms such as fluid retention, ascites, portal hypertension and jaundice often associated with severe liver disease
These symptoms may require treatment (not covered)
Hepatic encephalopathy
Neuropsychological syndrome seen in 70% of patients with cirrhosis
30-45% will develop severe
End stage liver failure 30% will be severe- coma
Characteristic of acute liver failure
what are the 3 stages of alcoholic liver disease
3 Recognised stages
Stage 1: Alcoholic fatty liver disease
Normally asymptomatic can occur rapidly
Normally reversible by taking a break from drinking
Stage 2: Alcoholic hepatitis
Mainly due to chronic use over a long period
Progression can be halted by stopping drinking
Stage 3: Cirrhosis
Unlikely to survive (<5 years)unless stop drinking permanently
what is the management of alcoholic liver disease?
STOP DRINKING ALCOHOL!
may require many support services, pharmaceutical interventions
Reducing alcohol intake, changing behaviour may be enough in early stages (before Alcoholic hepatitis)
Can treat some serious symptoms of alcohol withdrawal
Delirium Tremens (DTs)
- diazepam
Malnutrition and thiamine deficiency - Wernicke’s encephalopathy
IV thiamine
Vitamin supplements
what is the stages of Non-Alcoholic fatty liver disease (NAFLD)
No specific blood tests – further investigations required
linked to obesity
Stage 1: Fatty liver (~20% population)
Asymptomatic, may be detected by LFTs
Stage 2: NASH (Non-Alcoholic SteatoHepatitis)
Inflammation possibly pain
~2-5% population
Stage 3: Fibrosis
Stage 4: Cirrhosis
Patients at risk:
Diabetes Type II, Obese, Hypertension, Hypercholesterolemia, smokers, over 50
what is the management for NAFLD / NASH
Currently no NICE guidance on how to treat
No Specific medication
Increase in exercise and improve diet
esp. overweight/diabetic
Treat underlying cause:
E.g. Better control of Diabetes /hypertension/ cholesterol
Avoid/reduce alcohol intake
what does hepatitis mean
inflammation in the liver
Hepatitis A
causes
symptoms
treatment
Transmission:
faecal-oral route;
Consumption contaminated food (e.g.shellfish)
Also: sex (esp anal), sharing of needles
Symptoms:
Initial: nausea, vomiting, diarrhoea, malaise, abdominal discomfort, mild fever
jaundice, liver enlargement, skin rash/itch and pale stools
acute, self-limiting (3-6 weeks)
no treatment required –avoid alcohol while ill
Vaccination is available
Travel high risk areas, high risk groups
Hepatitis B
causes
symptoms
management
Transmission:
contracted from infected blood products (needles and tattooists),
sexual intercourse or mother-baby during birth
Symptoms
Similar to hepatitis A
Symptoms may take 1 to 3 months to present
Normally Self limiting
Blood test required for confirmed diagnosis
3-5% of patients progress to chronic hepatitis and require treatment with anti-viral drugs (see PM3A) of those 20% may progress to cirrhosis
Prevention advice:
Avoid high risk activities (e.g. unprotected sex, needle sharing)
Vaccination for risk groups (Active immunisation)
Health workers, drug injectors, people who change sexual partners frequently
If high risk exposure occurs:
active immunisation with passive immunisation occurs i.e vaccination for Hep B specific hepatitis B immunoglobulin (HBIG)
Hepatitis C
causes
symptoms
management
infected blood and blood products
Most cases in UK are IV drug users (about 50% have Hep C)
Rarely from unprotected sex
Generally asymptomatic or mild until develop chronic liver disease and/or cirrhosis - commonly diagnosed at this stage.
Diagnosis confirmed only by Hep C blood test
Treatment aims at achieving sustained viral clearance and uses anti-viral drugs that inhibit viral replication (i.e. pegylated INF-alpha and ribavirin – covered in greater detail in PM3A).
Up to 90% cure rate but no immunity
No Vaccine
what can paracetamol toxicity cause?
Overdose can cause permanent liver damage and death
Leading cause of acute liver failure in the UK
Most commonly taken overdose in suicide attempts
Maximal recommended dosage for an adult 4g in 24h*****
1g - per 4-6h interval
Overdose and liver damage can occur with as little as 10-15g!
High risk patients could be as low as 5g
what is used to treat paracetamol toxicity (drug name)
N-acetylcysteine
Within 1 hour - Activated charcoal adsorbs drug in GIT
Acetylcysteine treatment IV
Treat if on or above treatment line
Staggered dose/doubt timing TREAT
100% effective if given <8hours less >8h
>24h from overdose to 1st presentation National poisons service to be notified
what is the management for paracetamol toxicity
Always refer suspected overdose to A&E
Often initially asymptomatic, LFT normal
Nausea vomiting fatigue
must not be discharged without treatment
Establish timing of overdose
Severe liver damage after 24hours- unlikely to be reversible
Liver failure 48-96 hours after overdose
Interpret paracetamol levels
Timed serum paracetamol level 4-15h after ingestion
<4 h cannot be interpreted
>15 h liver damage may affect interpretation
what pharmokenetic considerations need to be taken when prescribing
Liver disease seriously affects metabolism and duration of action of drugs
Prescribing should be kept to a minimum
Due to large capacity of the liver often only apparent in severe liver disease
Problems more likely if symptoms such as jaundice , portal hypertension, ascites
Some drugs (rifampicin and fusidic acid) are excreted unchanged by the liver and should be avoided May change the concentration of a drug that is considered hepatotoxic Relevant warnings are found for each drug in the BNF
relationship of hepatic blood flow with pharmakenetic
In liver disease hepatic blood flow can be reduced
Bioavailability of drugs in drugs going 1st pass metabolism increased
Drugs that have high extraction via 1st pass may need to have dose adjusted
E.g. morphine may require dose 10-50% lower
Portosystemic shunting
Reduced 1st pass metabolism
what does low serum albumin cause / hypoproteinaemia ?
Low Serum Albumin (protein produced by the liver)
Albumin main site of drug binding in plasma
Increased concentrations of free drug
Important for drugs that bind strongly to plasma proteins
E.g. Warfarin, phenytoin
Reduced clotting factors
Increased sensitivity to anticoagulants (e.g. warfarin) - either reduce or stop
Increased fluid retention/Ascites
Worsened by drugs that cause fluid retention (e.g. NSAIDs glucocorticoids)
what can sedative drugs do?
Sedative drugs action may be increased in liver disease
Could mask Hepatic encephalopathy
what drugs should be avoided
NSAIDS, warfarin to be avoided
what are lft follow up
Further investigations
Imaging - scans of liver
Biopsy - key hole surgery and taking a small sample of liver and testing
Further blood tests (e.g. for hepatitis)
- Follow Progression
- Monitor response to treatment (incase you are giving the wrong medication )
FURTHER TESTS:
Further Blood tests e.g. for viral infection
Liver biopsy
Invasive -Local anaesthetic,
histology and pathology performed
Most reliable diagnostic tool for confirming liver damage
Imaging
Generally ultrasound - often prior or with to biopsy
CAT scan
Other investigations
Laparoscopy
Endoscopy
what are the standard lfts?
enzyme tests : ALT alanine transaminase AST aspartate transaminase ALP alkaline phosphatase GGT gamma glutamyltransferase
protein tests:
Bilirubin
Albumin
Prothrombin (clotting)
standard lft test?
what does Amino transferases: AST (aspartate transaminase) and ALT (alanine transaminase) show?
Amino transferases: AST (aspartate transaminase) and ALT (alanine transaminase)
Inflammation indicators
Damaged hepatocytes release both into blood stream
Highest in viral infection
High levels in drug induced, viral, ischaemic and autoimmune hepatitis
ALT more specific to liver (AST may indicate damage on muscle)
AST: ALT ratio:
>2 indicates alcoholic liver disease
<1 indicates non-alcoholic liver disease
standard lft?
What does ALP (alkaline phosphatase) measure?
ALP (alkaline phosphatase)
marker of bile function
Raised ALP and GGT may indicate block of bile ducts
GGT level useful for detecting alcohol damage
Small amounts of alcohol can alter test results
But high GGT can be for any form of liver damage
Combination of GGT with ALT helps to confirm liver is source of raised ALT
standard lft?
What does GGT (gamma glutamyltransferase) measure?
liver damage indicator
Raised ALP and GGT may indicate block of bile ducts
GGT level useful for detecting alcohol damage
Small amounts of alcohol can alter test results
But high GGT can be for any form of liver damage
Combination of GGT with ALT helps to confirm liver is source of raised ALT
standard lft?
What does Bilirubin measure?
Total Bilirubin
Breakdown product of haemoglobin
Causes jaundice (yellow of skin/ eyes)
Levels in blood may predict liver disease
Conjugated Bilirubin
Measure of liver function as liver conjugates bilirubin
Generally used to ascertain if bilirubin is being produced beyond capacity of liver to conjugate
standard lft?
What does albumin measure?
Albumin
Synthesized by liver,
Normally responsible for oncotic pressure in blood and transport/binding of nutrients and drugs
Decreases may cause fluid retention and indicate liver disease
Severe deficit in albumin may also be due to malnutrition (possible in alcohol dependence)
what can changes to total protein in lft show?
Total Protein
Normally normal in liver disease, but changes may indicate a malnutrition (common in alcohol dependancy)
clotting factors:
prothrombin and prothrombin time - what does these show ?
(INR)
Prothrombin and prothrombin time
Time taken for blood to clot following sample
Longer PT time indicates reduction in clotting factors produced by liver
vitamin K deficiency (malnutrition/block of bile extraction)
Normally expressed as INR (International Normalised Ratio)
Standardised version of PT
Target normally 2-3, higher values indicate reduced clotting
With high PT/INR score may be repeated following injection of vitamin K
