(SYNOPTIC) Liver Disease & Management Flashcards
What percentage of the liver is comprised of hepatocytes?
60%
How many blood supplies does the liver have?
2
Hepatic artery (from heart) Portal vein (blood from the bowel)
What are the functions of the liver?
(1) Metabolism
(2) Synthesis
(3) Immunological
(4) Storage
(5) Secretion
(6) Homeostasis
What are some examples of substances metabolised in the liver?
- Products of digestion
- Bilirubin
- Steroid hormone
- Insulin
- Aldosterone
- Vitamin D
What is synthesised in the liver?
- Plasma proteins
- Clotting factors
- Cholesterol
- Urea (from amino acids)
What is stored in the liver?
- Fat soluble vitamins
- Glycogen
- Blood reservoir
What is secreted in the liver?
Bile + bile salts
What is the function of the liver in homeostasis?
Glucose regulation
Conversion of glucose to glycogen
What are some potential causes for chronic liver disease?
- alcohol
- NAFLD/ NASH
ø Non-alcoholic fatty liver disease - immune/ autoimmune
- drugs
- malignancy
- HCV/ HBV
ø Hep C + Hep V
What are some potential causes for acute liver disease?
- HAV/ HBV/ HEV ø 3rd trimester of pregnancy - Drugs - TPN - Infection, e.g. malaria - Ischaemia - Alcoholic hepatitis - Acute fatty liver of pregnancy
What increases risk of non-alcoholic fatty liver disease?
- T2DM
- Obesity
- Dyslipidaemia
What may be the first presentation of NAFLD?
Cirrhosis
What is the non-pharmacological management of NAFLD?
- Weight loss
- Healthy diet
- Exercise
- Smoking/ alcohol cessation
- 2-3 cups of black coffee daily
What is the pharmacological management of NAFLD?
- Statins
- Treat HTN/ T2DM
What co-morbidities can make a HepC (HCV) infection worse?
(1) HIV
(2) Underlying cirrhosis
(3) Liver transplant
(4) Lifestyle
What is the process of chronic liver disease development?
(1) Insult
- e.g. toxin/ virus
(2) Hepatitis or steatohepatitis
(3) Reversible
- if cause is stopped, e.g. alcohol cessation
(4) If insult is not removed
(5) Fibrosis
- scarring + thickening of smooth muscle
(6) Cirrhosis
What is the general classification of liver disease?
(1) Compensated
- Asymptomatic due to medication/ sufficient healthy liver tissue for normal function
(2) Decompensated
- Symptomatic
What is a liver function test?
Used to identify patients struggling with liver/ biliary tract disease
What is a downside of liver function tests when checking for liver disease?
Some LFTs reflect liver DAMAGE rather than function
What results from a liver function test are considered a cause for concern?
3 times the upper limit of normal
How should a liver function test be used?
(1) Look for trends
(2) Do not use in isolation
What would a liver function test (LFT) show in acute hepatocellular damage?
HIGH - plasma ALT HIGH - plasma AST HIGH - bilirubin (unconjugated) PROLONGED - prothrombin time NORMAL - albumin
What would a liver function test (LFT) show in chronic hepatocellular damage?
NORMAL - ALT
NORMAL - AST
LOW - albumin
PROLONGED - prothrombin time
What would a liver function test (LFT) show in cholestasis (blockage of bile duct)?
HIGH - plasma ALP
HIGH - bilirubin (conjugated)
What other investigations can be done alongside a liver function test (LFT)?
(1) Ethanol
(2) Drug history
(3) FBC
(4) Clotting
(5) U+Es
(6) Liver ultrasound
(7) Biopsy
(8) Liver screen
- if obstruction ruled out
- check for viral causes
How is acute liver failure graded?
(1) Hyperacute
- 6-7 days
(2) Acute
- 8-28 days
(3) Subacute
- 29-84 days
In which liver failure grade(s) is cerebral oedema rare?
Subacute
In which liver failure grade(s) is cerebral oedema common?
Hyperacute/ acute/ subacute
(1) Hyperacute
(2) Acute
What is the prognosis for each liver failure grade?
Hyperacute - moderate
Acute - Poor
Subacute - Poor
What is used to grade chronic liver disease?
(1) Child’s Pugh Score
(2) MELD
- Model for end-stage liver disease
- OR UKELD
What are the grades for chronic liver disease using the Child’s Pugh Score?
(1) A 5-6 points COMPENSATED
(2) B 7-9 MODERATE
(3) C 10-15 ADVANCED
What is the MELD score used for?
Determining the mortality of end-stage liver disease
What are some common symptoms of liver disease?
(1) Jaundice - yellowing of eye
(2) Spider nevi in upper chest
(3) Ascites - accumulation of fluid in peritoneal cavity
(4) Clubbing of nails
(5) Dilated abdominal veins
(6) Ankle oedema
(7) Bleeding tendency due to decreased prothrombin time
Which blood vessel brings blood to the liver from the heart?
Hepatic artery
Which blood vessel brings blood to the liver from the bowel?
Portal vein
How many general functions of the liver are there?
6
What are the general functions of the liver?
(1) Homeostasis
(2) Storage
(3) Metabolism
(4) Immunological
(5) Secretion
(6) Synthesis
Name some causes of chronic liver disease.
- Alcohol
- NASH/ NAFLD
- Drugs
- Malignancy
- Autoimmune
- HCV/ HBV
- Metabolic, e.g. haemochromatosis
Name some causes of acute liver disease.
- Drugs
- TPN
- Ischaemia
- Infection
- Alcoholic hepatitis
- Acute fatty liver of pregnancy
What is non-alcoholic fatty liver disease?
A range of liver diseases
From simple fatty liver -> Non-alcoholic seato-hepatitis -> Fibrosis/ cirrhosis
What are some risk factors for NAFLD?
- Diabetes
- Obesity
- Dyslipidaemia (metabolic syndrome)
What is the non-pharmacological management for NAFLD?
- Weightloss
- Healthy diet
- Exercise
- Stop smoking/ alcohol
- 2-3 cups of black coffee daily
What is the pharmacological management for NAFLD?
- Treat BP
- Treat diabetes
- Statins
What patient groups are at higher risk of Hepatitis B?
- IV drug users
- Casual sex
- Close family members
- Babies born to infected mothers
- HCPs
What are the stages of progression of chronic liver disease?
(1) Insult
- e.g. toxin/ virus
(2) Hepatitis/ steatohepatitis
(3) Reversible
- liver is regenerating
(4) Insult not removed
(5) Fibrosis
- thickening + scarring
(6) Cirrhosis
- chronic liver disease
What is compensated chronic liver disease?
Asymptomatic
Sufficient meds/ tissue to continue normal function
What is decompensated chronic liver disease?
Symptomatic
What result of a LFT is considered to be cause for concern?
3x upper limit of normal
What LFT results would be expected in acute hepatocellular damage?
- Large rise in ALT + AST
- 2y rise in unconjugated bilirubin
- Prolonged PT
- Normal albumin
What LFT results would be expected in chronic hepatocellular damage?
- Fairly normal ALT + AST
- Prolonged PT
- Low albumin
What LFT results would be expected in cholestasis?
- Rise in ALP
- Rise in conjugated bilirubin
What is cholestasis?
Blockage of the bile duct
Name some other investigations that can be carried out to determine liver damage/ function, alongside LFTs.
- Ultrasound of liver
- Biopsy
- Liver screen (if known no obstruction)
What are the grades of acute liver failure?
(1) Hyperacute
(2) Acute
(3) Subacute
How many grades of acute liver failure are there?
3
What is the time from jaundice to encephalopathy in hyperacute liver failure?
6-7 days
What is the time from jaundice to encephalopathy in acute liver failure?
8-28 days
What is the time from jaundice to encephalopathy in subacute liver failure?
29-84 days
In which grades of acute liver failure is cerebral oedema common?
- Hyperacute
- Acute
When does renal failure occur in hyperacute liver failure?
Early
When does renal failure occur in acute liver failure?
Late
When does renal failure occur in subacute liver failure?
Late
What is ascites?
Abnormal fluid buildup in the abdomen.
In which acute liver failure types is coagulation disorder considered marked?
Hyperacute and acute
What is the prognosis of hyperacute liver failure?
Moderate
What is the prognosis of acute liver failure?
Poor
What is the prognosis of subacute liver failure?
Poor
What is the Child’s Pugh Score used for?
Grading of chronic liver disease (cirrhosis)
How is cirrhosis graded?
(1) Child’s Pugh Score
(2) MELD/ UKELD
Name some symptoms of liver cell failure.
- Coma
- Spider nevi
- Gynecomastia
ø enlargement of male breasts - Jaundice
- Ascites
- Loss of sexual hair
- Testicular atrophy
- Bleeding tendency
ø decreased prothrombin - Anaemia
- Ankle oedema
Name some symptoms of portal hypertension.
- Oesophageal varices
- Gastropathy
ø melaena - Splenomegaly
- Dilated abdominal veins
- Ascites
- Haemorrhoids (rectal varices)
What are some causes of ascites?
- Impaired aldosterone metabolism
- Low albumin
- Reduced renal blood flow
- Portal hypertension
- Increased hepatic lymph production
Which drugs, generally, can exacerbate ascites and peripheral oedema?
- NSAIDs
- Salt
- Saline
What is the treatment for ascites?
(1) Fluid + salt restriction
(2) Spironolactone
- aldosterone antagonist
(3) Furosemide
- for peripheral oedema
(4) Paracentesis
- Removal of peritoneal fluid
(5) TIPSS
- connect portal vein to hepatic vein in the liver
(6) Peritoneo-venous shunt
- peritoneal fluid from peritoneum into veins
What is hepatic encephalopathy?
Reversible changes in mental state
2y to failure of liver, due to inability to metabolise toxins
What are the stages of hepatic encephalopathy?
(1) Forgetfulness/ confusion/ agitation
- >
(4) Coma + unresponsive to painful stimulus
How many stages of hepatic encephalopathy are there?
4
What is the treatment of hepatic encephalopathy?
- Remove/ avoid precipitants
- Reduce protein intake
- Decrease bacterial ammonia production
- Increase elimination of bacteria ammonia production
What is the pharmacological treatment for hepatic encephalopathy?
(1) Lactulose
- prevents constipation, inhibits colonic bacteria
(2) Phosphate enemas
(3) Rifaximin
- poorly absorbed Abx, eliminates colonic bacteria
What is pruritus?
Severe itching of the skin
How does chronic liver failure cause pruritus?
- Bile acid build up in the skin
What is the pharmacological treatment for pruritus, secondary to liver failure?
(1) Chlorphenamine, be careful due to masking hepatic encephalopathy
(2) Menthol in aqueous cream
How is VTE risk evaluated in liver failure?
PT
Prothrombin time
Which administration route should be avoided in VTE, secondary to liver failure?
IM
Can lead to haematoma
What is a variceal haemorrhage?
Bleeding of varices in GIT
What causes a variceal haemorrhage?
(1) Decrease blood flow through liver
(2) Portal HTN (>12mmHg)
(3) Collateral vessels
(4) GIT varices
What is DILI?
Drug induced liver injury
What are the types of DILI?
(1) Type A - intrinsic
(2) Type B - idiosyncratic
Describe Type A (intrinsic) DILI (drug induced liver injury)
- Predictable
- Dose related
- Occurs rapidly
- Causes necrosis/ acute liver
- Can occur at lower doses if LD already
- Direct toxicity of drug/ metabolite
- Often identified in clinical trials
- Reproducible in animal models
Describe Type B (idiosyncratic) DILI.
- Unpredictable
- May/ may not be dose related
- Tends to take longer to occur (weeks->months)
- Often more frequent if pre-existing LD
- Accounts for >90% of cases
What website/ source can be used to identify causative agent(s) of drug-induced liver injury (DILI)?
LiverTox
What drug class has the highest incidence for causing DILI?
Antimicrobials
What drug class has the second highest incidence for causing DILI?
Herbal and dietary supplements
Which metabolite of paracetamol is toxic?
NAPQI
What is the antidote for paracetamol?
N-acetylcysteine
What are inducers of P450 enzymes in the liver?
- Carbamazepine
- St John’s Wort
- Phenytoin
- Rifampicin
- Ethanol
What are inhibitors of P450 enzyme in the liver?
- Erythromycin
- Amiodarone
- Protease inhibitors
- Ciprofloxacin
What are some prescribing tips for drugs and the liver?
- Most drugs are safe in stable liver disease
- Use older + more established drugs
- Avoid drugs
- Start with small dose and increase slowly
- Choose best option and monitor clinical response
Which analgesics should be actively avoided in hepatic impairment?
NSAIDs + COX2 inhibitors
For which analgesics should there be caution when used in hepatic impairment?
Opioids
e.g. codeine is metabolised to active form in the liver
Are tricyclic antidepressants suitable in hepatic impairment?
Yes, at low doses
How should neuropathic pain be treated in hepatic impairment?
Gabapentin is suitable
What should be the antidepressant choice in hepatic impairment?
- Sertraline/ citalopram
- TCAs should be avoided due to sedating effect
- Mirtazepine is also suitable, due to low bleeding risk but has a sedating effect
When should statins be avoided in hepatic impairment?
(1) Acute liver disease
(2) Decompensated chronic liver disease
How can seizures from alcohol withdrawal be prevented?
Benzodiazepine
- Chlordiazepoxide
- Diazepam
- Lorazepam
What is chlordiazepoxide?
Anxiolytic + anticonvulsant
When should a chlordiazepoxide dose be reassessed, when used in alcohol withdrawal?
If >3 PRN doses are required in 24hrs
On a flexible chlordiazepoxide regimen, for alcohol withdrawal, what should the review criteria be?
Calculate every 2-4hrs depending on severity
Is this drug long, intermediate, or short-acting? Diazepam
Long-acting
Is this drug long, intermediate, or short-acting? Lorazepam
Short/ intermediate-acting
Is this drug long, intermediate, or short-acting? Oxazepam
Short/ intermediate-acting
Is this drug long, intermediate, or short-acting? Chlordiazepoxide
Long-acting