Liver Disease Flashcards
What are some of the causes of liver disease?
Alcohol (approx. 50-70% of cirrhosis is alcohol related)
Non-alcoholic fatty liver disease (NAFLD)
Viral hepatitis
Drugs and toxins
Inherited and metabolic disorders (e.g. Wilsons disease)
Immune disease of the liver (e.g. autoimmune hepatitis)
Vascular abnormalities (e.g. Budd-Chiari syndrome)
Cancer
Biliary tract disorders
Infection
The liver is the _ single organ excluding _.
Largest
The skin
How is the liver supplied with blood?
Has 2 blood supplies,
Arterial blood - 20%, hepatic artery
Venous blood - 80%, portal vein
The liver has a remarkable ability for _.
Regeneration
What are some of the functions of the liver?
Metabolism including carbohydrate, protein, fat, steroid hormone, insulin, aldosterone, bilirubin and drugs
Synthesis including proteins, clotting factors, fibrinogen, cholesterol, 25-OH of vitamin D and glucose from fat and protein
Immunological through Kupffer cells
Storage including fat soluble vitamins, A, D, K B12 and folic acid
Homeostasis through glucose control
Production of bile, secretion of bile salts and enterohepatic circulation
Clearance including bilirubin, drugs and toxins
How can we diagnose liver disease?
Using liver blood tests (previously called LFT’s but renamed as they don’t exactly reflect the function of the liver)
What do liver blood tests cover?
Bilirubin Transaminases ALP and γ-GT Albumin PT/INR
What is the usual range for bilirubin?
5-20 micromol/L
What is bilirubin?
Product of RBC breakdown
How does bilirubin reach the liver and what happens once it does?
Transported to the liver in the serum attached to albumin
Once in the liver, transformed into a water-soluble conjugate which is then excreted via the bile into the intestine
What do raised bilirubin levels suggest?
Haemolysis
Hepatocellular damage
Cholestasis
What level does a patients bilirubin have to be for them to be clinically jaundice?
> 50 micromol/L
What are the transaminases relevant to liver blood tests?
Aspartate transferase (AST) Alanine transferase (ALT)
What is the usual range for AST and ALT?
AST 0-40 iu/L
ALT 5-30 iu/L
Where are AST and ALT found?
AST is found in the liver, heart, skeletal muscle, pancreases, kidney and RBC’s
ALT is found primarily in the liver, often termed ‘liver specific enzyme’
What do raised AST and ALT levels suggest?
Hepatitis (inflammation)
Drugs
Sepsis
Do all patients with liver disease have raised transaminase enzymes?
No
Patients with severe liver disease may not have raised levels of transaminases as their cells are so damaged they can no longer produce transaminases
What is ALP?
Alkaline phosphatase
What is the usual range for ALP?
30-120 iu/L
Where can ALP be found?
In the liver, bone, intestine and placenta
What do raised ALP levels suggest?
Cholestasis
Damage to biliary tree
What is γ-GT?
γ-Glutamyltransferase
What is the usual range for γ-GT?
5-55 iu/L
Where can γ-GT be found?
In the liver and biliary epithelial cells, pancreas, kidneys, prostate and intestine
What do raised γ-GT levels suggest?
Cholestasis
Carcinoma of pancreas and GIT
Presence of enzyme inducers such as alcohol
What is albumin a marker of?
How well the liver is functioning as it is one of the proteins synthesised by the liver
What is the usual range for albumin?
35-50 g/dL
What is the half-life of albumin?
20-26 days (long)
What do decreased albumin levels suggest?
Oedema
Chronic liver disease (albumin has a long half life and so won’t be decreased straight away)
What is PT?
Prothrombin time
What is INR?
International Normalised Ratio
What are the usual ranges for PT and INR?
PT <16 secs
INR <1.2
Why are PT and INR indicators of liver function?
Because clotting factors are synthesised in the liver
What is the half-life of prothrombin?
2-3 days (short)
What do raised PT/INR levels suggest?
Acute and chronic liver disease
When are liver blood tests considered ‘abnormal’?
If the level is 2x the upper limit of what is considered normal
What needs to be taken into account when interpreting liver blood tests?
They are fairly non-specific
Need to look at trends amongst the results rather than look at them in isolation
Usually at least 2 will be deranged if there is liver dysfunction
Always check reference ranges and units
Blood tests are not always abnormal and similarly abnormal liver blood tests are not necessarily because of liver dysfunction
How is liver disease classified?
According to both the pattern of disease seen and the time course over which the damage occurs
When is liver disease considered acute?
Onset of symptoms does not exceed 6 months
When is liver disease considered chronic?
Symptoms exceed 6 months
The main patterns of damage can be initially classified as…
Cholestatic or hepatocellular
These are not distinct entities, overlap occurs
Both can lead to fibrosis or cirrhosis
What is cholestasis?
Elevated levels of substances usually excreted via bile, this leads to symptoms such as jaundice, pruritus
What does cholestasis affect?
Absorption of fat soluble drugs and vitamins
What is cholestasis caused by?
Disruption of bile blow e.g. stagnation of bile in bile ducts
Intrahepatic causes such as problems with biliary ductiles caused by primary biliary cholangitis (PBC), drugs, inflammation
Extrahepatic causes such as mechanical obstruction caused by inflammation of bile ducts, strictures or gall stones
How does cholestasis affect liver blood tests?
Increase in bilirubin, ALP, γ-GT (linked to biliary tree)
What is hepatocellular damage?
Injury to hepatocytes (liver) cells e.g. by toxins, viruses
What can hepatocellular damage lead to?
Steatosis (fat inside or outside liver cells)
Hepatits (inflammation)
Hepatocellular damage can be…
Acute or chronic
Small or widespread
How does hepatocellular damage affect liver blood tests?
Increase in transaminase enzymes, γ-GT, bilirubin (later)
What is fibrosis?
Persistent, extensive hepatocyte damage
Active deposition of collagen formation of scar tissue
What is cirrhosis?
When erratic regeneration occurs and nodules can form
Which comes first, fibrosis or cirrhosis?
Fibrosis
The spectrum of liver damage is…
Not uniform
There are 3 main histological stages, in reality these stages may overlap
What are the 2 main routes of alcohol metabolism?
Alcohol metabolised (by oxidation) to acetylaldehyde
Acetylaldehyde is then metabolised to acetate by aldehyde dehydrogenase
Acetate is then further metabolised to water, fatty acids and carbon dioxide
The ‘microsomal ethanol oxidising system’ is activated when high quantities of alcohol are taken in, this produces unstable free radicals
_ _ will increase metabolism of alcohol and drugs metabolised via this route.
NB 2E1 induction
What scoring system in cirrhosis?
Child’s Pugh Scoring System
Gives you an indication of how severe the patients cirrhosis is and classifies it into 3 classes, A, B and C, dependent on score, with C being the most advanced
What are the most common causes of acute liver disease?
Viral hepatitis and drugs
Does acute liver disease always progress?
Not always, but can go on to acute liver failure or chronic liver disease
What is meant by the term ‘compensated’?
Enough hepatocyte capacity to perform functions
What is meant by the term ‘decompensated’?
Do not have enough capacity to perform required liver functions
What are the most common causes of chronic liver disease?
Alcohol and chronic viral hepatitis
How can we manage chronic liver disease?
Treat the underlying condition where possible
Treat symptoms and complications
Surveillance for hepatocellular carcinoma (HCC)
Transplant may be the only option for some patients
Where are complications most commonly seen?
In chronic liver disease
How does complication management vary based on the cause of liver disease?
Management of complications remains the same regardless of the cause of liver disease
Do all patients with liver disease have symptoms?
No, many patients will be asymptomatic
Can be a long time interval between disease occurrence and detection as a result
What are some of the initial, unspecific symptoms of liver disease?
Fatigue
General malaise
Fever
N&V
What are some of the later, more specific symptoms of liver disease?
Jaundice Pale stools Dark urine Pruritus Spider naevi Bruising and bleeding Gynaecomastia Liver palms Finger clubbing Ascites Varices Encephalopathy (Last 3 generally seen in end stage liver disease)
What is jaundice caused by?
High levels of bilirubin
What do pale stools indicate?
Biliary obstruction
Usually bile is excreted into the intestine where it is converted to the faecal pigment stercobilin
If there is obstruction, bile excretion is reduced, and so less pigment is produced
What does dark urine indicate?
Obstruction
Water soluble conjugated bilirubin can’t be excreted in faces and therefore body compensates by increasing renal excretion
What are ‘spider naevi’?
Vascular changes
What is gynaecomastia?
Enlargement of the male breast tissue
What does gynaecomastia indicate?
Impaired metabolic function
Increased levels of oestrogen as reduced oestrogen degradation in chronic liver disease
What is gynaecomastia also a side effect of?
Spironolactone
Inhibition of testosterone production
What is ascites?
Presence of excess fluid in the peritoneal cavity leading to a swollen abdomen
What does ascites cause?
An excess of sodium in the body
How can ascites be treated?
Restrict fluid/sodium intake
Diuretics e.g. spironolactone, furosemide
Paracentesis for large volumes (involves inserting a drain and draining off ~8-10L of liquid)
Why is spironolactone 1st line for diuretics in the liver patients?
It is an aldosterone antagonist and liver patients will have higher levels of aldosterone
How should patients suffering from ascites be monitored?
Weight (aim for 0.5-1kg weight loss/day)
Daily U&E’s especially Na, K, Cr (you’re using high doses of diuretics, electrolytes will be affected)
What is spontaneous bacterial peritonitis?
Infection of the ascitic fluid without intra-abdominal source of sepsis
A frequent complication of ascites
How is spontaneous bacterial peritonitis diagnosed?
Neutrophil count >250 cells per mm3
How is spontaneous bacterial peritonitis treated?
With a broad spectrum IV antibiotic e.g. 3rd generation cephalosporins, co-amoxiclav, tazocin
What can be given for spontaneous bacterial peritonitis prophylaxis?
Norfloxacin
Ciprofloxacin
What is hepatic encephalopathy?
Neuropsychiatric changes including changes in mood and behaviour, confusion, delirium and coma
4 different grades dependent on clinical signs
What causes hepatic encephalopathy?
Accumulation of toxins especially ammonia (this is why a lot of treatments are targeting at reducing ammonia levels)
What are some precipitants of hepatic encephalopathy?
Increased protein load Accumulation of ammonia Electrolyte disturbance Drugs Infection
Symptoms of hepatic encephalopathy are similar to?
Hypoglycaemia
Alcohol intoxication or withdrawal
How is hepatic encephalopathy treated?
Want to avoid precipitants and reduce ammonia levels
Laxatives are the mainstay of treatment (aim for 2-3 soft stools per day) e.g. lactulose liquid, phosphate enema
Antibiotics e.g. Rifaxamin
L-ornithine L-aspartate sachets
Why is Rifaxamin used in hepatic encephalopathy treatment?
It has low systemic absorption meaning high levels in faeces, it kills gut bacteria to reduce amino levels (gut bacteria produce ammonia)
Why is L-ornithine L-aspartate used in hepatic encephalopathy treatment?
Part of the urea cycle
Increases removal of ammonia
What is portal hypertension and what is it caused by?
An increase in pressure in the portal vein
This is caused by increased resistance to flow due to,
Disruption of hepatic architecture
Compression of hepatic venules by regenerating nodules
How does the body respond to portal hypertension?
Forms collateral vessels, enables blood to bypass the liver
Works temporarily, but eventually as the liver condition worsens, and pressure rises, these weak blood vessels burst and bleed out (bleeding varices)
How can portal hypertension/ bleeding varices be treated?
Resuscitation with fluids and blood transfusion
Endoscopy to perform banding (putting tiny elastic bands on vessels) or sclerotherapy (glueing the collateral vessels)
Terlipressin can be used as a temporary fix, a potent vasoconstrictor (reduces pressure around the liver)
Antibiotics as infection is common in liver patients, IV broad spectrum
PPI
What can be given as secondary prophylaxis for portal hypertension/ bleeding varices?
Propanolol tablets 20-40mg BD
A non-selective beta blocker
Works in GI system to lower pressure around the liver
Low doses given as propranolol is extensively first pass metabolised and this will not happen as effectively
What causes pruritus?
Accumulation of bile salts under the skin as they are not excreted
How can pruritus be treated?
Colestyramine (binds bile acids and prevents reabsorption, anion-exchange resin)
Ursodeoxycholic acid (works on how bile acids are broken down)
Antihistamines e.g. chlorpheniramine
Topical treatments e.g calamine lotion
Ondansetron, Rifampicin, Naltrexone, Naloxone (not usually associated with treating itching but have been found to help in some patients)
What are some of the symptoms of alcohol withdrawal?
Delirium Marked terror Fear and delusions Restlessness and agitation Fever Rapid pulse Dehydration Seizures
How are symptoms of alcohol withdrawal treated?
Treated with a combination of sedatives and vitamin supplementation e.g. Chlordiazepoxide and Pabrinex IV or oral vitamin B co strong and thiamine
Why is Chlordiazepoxide used in the treatment of alcohol withdrawal?
Sedative and anti-convulsant properties Long half-life (5-30 hours) Extensively protein bound (96%) Low potency Slower onset of action (less abuse potential) Long acting
How should Chlordiazepoxide be prescribed?
With an oral reducing regimen and given as needed by patient in a detoxification regimen
Why do people experiencing alcohol withdrawal need vitamin supplementation?
To treat a potential thiamine deficiency
Thiamine deficiency can cause Wernicke’s encephalopathy (irreversible)
Alcohol prevents thiamine absorption (causes malabsorption in the intestine mucosa)
Alcoholics are also often vitamin deficient due to a poor diet (high in carbohydrate, low in protein, vitamins and minerals)
Viral hepatitis can be…
Acute or chronic
Viral hepatitis is caused by…
Hepatitis A, B, C, D or E virus
What is the commonest form of infective hepatitis?
Hepatitis A
How is hepatitis A transmitted?
Primarily enterically transmitted (faecal-oral route)
Is hepatitis A serious and how does it progress?
Usually mild and does not progress to chronic liver disease or carrier status
For which types of viral hepatitis is there a vaccine?
A, B
What is the structure of the hepatitis B virus and how does it infect cells?
An enveloped DNA virus (hepadnavirus)
Incorporates itself into cells making it difficult to treat (very similar to HIV)
Is hepatitis B contagious?
Highly
Present in blood, saliva, urine, semen and vaginal fluids
How is hepatitis B treated?
Clinical course is dependent on age of infection but it is usually difficult to eradicate and treatment revolves around trying to reduce levels
Also depends on age, extent of liver damage, virology and HBV DNA level
Oral antivirals e.g. Entecavir or Tenofovir are used (this is often long term for the majority of patients)
Pegylated interferon
What is the leading cause of hepatocellular carcinoma (HCC)?
Hepatitis B
What is hepatitis D also known as?
Delta virus
Hepatitis D can only replicate in the presence of…
Hepatitis B virus
What is the relationship between hepatitis D and B?
Acquired in the same way
Can get HDV at the same time as HBV (co-infection) or at a later date (superinfection)
Combination of the two increases the risk of progression to chronic hepatitis and cirrhosis
Treatments for HDV very similar to HBV
Hepatitis E has a similar clinical course to which other hepatitis virus?
HAV
How is hepatitis E transmitted?
Faecal-oral route
Is hepatitis E serious and how does it progress?
Usually mild and does not progress to chronic liver disease or carrier status
What is the structure of the hepatitis C virus?
Single stranded RNA virus of the Flavivirdae family (means it can be eradicated?
Hepatitis C is a…
Blood borne virus
How many major genotypes of hepatitis C have been identified?
6
How is hepatitis C diagnosed?
Testing for hepatitis C antibodies, HCV RNA and genotype
Majority of those infected are undiagnosed as it is largely asymptomatic
Hepatitis is C is known as the…
‘Silent killer’, a slow progressive disease
Is hepatitis C curable?
Yes
How is hepatitis C treatment selected?
Finite courses
Choice and duration dependent on genotype, extent of liver damage and treatment history
WHO aims to?
Eliminate HCV as a public health threat by 2030
In drug induced liver disease, does discontinuation of the drug result in resolution?
Generally, yes but not always the case
What is an intrinsic reaction (type A)?
Predictable
Reproducible
Would happen to everybody
Dose dependent
Tend to occur rapidly e.g. within hours
Tend to have necrosis, acute liver failure
An example of intrinsic/type A reaction is a paracetamol overdose
What is an idiosyncratic reaction (type B)?
Tends to be the vast majority of drugs
Not predictable
Not reproducible
Not dose dependent
Take longer to occur e.g. weeks to months
Can result from metabolism idiosyncrasy or immunoallergic reaction
Can cause any type of liver injury e.g. increased LFT’s, jaundice, fever, rash, eosinophilia
An example of an idiosyncratic/type B reaction is warfarin causing cholestasis
What is the role of the pharmacist in liver disease?
Ensure regular monitoring of LFT’s
Ensure patients and prescribers are aware of side-effects and warning signs
Take a full drug history including herbal, OTC
Be aware of drugs commonly implicated and how to manage this
Advise on management including supportive therapy
