Liver Disease

Question 1

Main functions of the liver

Answer 1

Central to maintenance of homeostasis
Storage
Clearance 
Filtration
Secretion
Excretion
Synthesis
Metabolism

Question 2

Methods of detoxification

Answer 2

Destroys endogenous and exogenous substances
Destroys cellular debris
Deamination of amino acids
Removal of bilirubin
Hormone deactivation

Question 3

Features of acute liver disease

Answer 3

Less than six months duration
Often resolves spontaneously, self limiting
Rapid decline in liver function
May be asymptomatic
100% association with encephalopathy and coagulopathy
Can result in acute liver failure

Question 4

Features of chronic liver disease

Answer 4

Over six months duration
Often symptomatic
Secondary to long-standing cell damage
Permanent structural change
Loss of normal liver architecture
Cirrhosis- fibrous scars, divides the liver into nodules

Question 5

Causes of liver disease

Answer 5

Viral infection- Hepatitis A-E
Alcohol
Non-alcoholic fatty liver disease
Non-alcoholic steatohepatitis
Cholestasis (intra-hepatic, extra-hepatic)
Immune disorders
Vascular abnormalities
Metabolic disorders
Genetic disorders

Question 6

Features of viral infection

Answer 6

Hep A- faecal contamination of food or drink
Hep B- blood/blood contamination
Hep C- blood/blood contamination
Hep D- have to have Hep B to get Hep D
Hep E- faecal contamination of food or drink

Question 7

Causes of liver disease- alcohol features

Answer 7

Single most significant cause of liver disease in the Western World
Eventually leads to cirrhosis
Fibrous tissue in liver increases resistance to blood flow from the portal system resulting in portal hypertension
As liver cell death continues, leads to liver failure
Rate of progression (and regression) linked to further alcohol consumption

Question 8

Drug related liver disease- type A

Answer 8

Dose related
Withdrawal of precipitating drug results in reversal
e.g. paracetamol, tetracyclines, methotrexate

Question 9

Drug related liver disease- type B

Answer 9

Idiosyncratic (related to a drug property)

Hypersensitivity or metabolic

Question 10

Symptoms of liver disease

Answer 10

Non specific symptoms- weakness, fatigue, general malaise
Poor nutrition status- weight loss, anorexia, loss of muscle bulk
Abdominal discomfort/ pain
Tenderness over liver
Jaundice

Question 11

Cutaneous symptoms of liver disease

Answer 11

Hyperpigmentation
Scratch marks
Spider naevi
Non-specific- palmar erythema, Dupuytren’s contracture, finger clubbing

Question 12

Abdominal signs of liver disease

Answer 12

Distension
Hepatomegaly (increase in liver size)
Splenomegaly (increase in splen size)
Umbilical and paraumbilical veins

Question 13

Jaundice

Answer 13

Does not automatically mean liver disease
Yellowing of skin and sclerae
Hepatocellular- drugs, hepatitis, tumour
Cholestatic- obstruction
Prehepatic- increased blood breakdown

Question 14

Pruritis

Answer 14

Deposition of bile salts in the skin
Concentration does not correlate with severity
Most debilitating in cholestatic conditions
Obstruction relieved by endoscopy, radiology, surgery
Pharmacological treatment favoured for other causes

Question 15

Portal hypertension

Answer 15

Increase pressure in portal venous system leads to collateral vein formation and shunting of blood to systemic circulation
Contributes to formation of ascites and development of encephalopathy
Complications- variceal bleed

Question 16

Ascites

Answer 16

Accumulation of fluid within the abdominal cavity

Caused by central hypovolaemia, reduced serum albumin, portal hypertension and splanchnic artery vasodilation

Question 17

Clotting abnormalities

Answer 17

Hepatocyte failure causes defective synthesis of clotting factors I and V, leading to increased tendency to bleed
Also leads to defective bile salt excretion, malabsorption of vitamin K and defective synthesis of II, VII, IX and X

Question 18

Sexual characteristics

Answer 18

Endocrine changes most common in alcoholic liver disease
Thought to be due to poor metabolism of oestrogen
Males- testicular atrophy, female body hair, gynaecomastia
Females- menstrual irregularity, reduced fertility

Question 19

Biochemical investigations

Answer 19

Simple, inexpensive, easy to perform
Useful to monitor disease progression or response to therapy
Enzymes- hepatocellular or cholestatic
Bilirubin
Synthetic function- clotting time

Question 20

Other investigations

Answer 20

Laboratory investigations- Hep A, B and C virology, immunoglobulins, lipid profile etc.
Imaging- ultrasound- preliminary assessment; CT and MRI- precise definition of abnormalities
Biopsy- gold standard for establishing diagnosis and assessing severity

Question 21

Treatment of pruritis

Answer 21

Anion exchange resins e.g. colestyramine, colestipol- bind bile acids and prevent reabsorption, side effects: GI, fat and vitamin malabsorption, poor adherence due to palatability
Counselling- take interacting drugs one hour before or four hours after colestyramine, benefits may take up to one week to become apparent
Antihistamines
Arsodeoxycholic acid
Topical therapies e.g. calamine lotion

Question 22

Treatment of ascites

Answer 22

Aim is to mobilise intra-abdominal fluid
Simple measures include reducing sodium intake and fluid restriction
Moderate to severe ascites requires diuresis or paracentisis (using needle to pull blood out)

Question 23

Pharmacological treatment of ascites

Answer 23

Diuretics
Spironolactone is first line agent- blocks sodium reabsorption in kidney tubules, 50-400mg daily, titrate slowly, causes gynaecomastia and hyperkalaemia, add furosemide if severe, acre to avoid excessive diuresis

Question 24

Paracentisis

Answer 24

Used in refractory ascites, combined with albumin administration, does not affect mechanisms responsible for fluid accumulation, repeated every 2-4 weeks in outpatient setting

Question 25

TIPS

Answer 25

Transjugular Intrahepatic Portosystemic Shunt | Prevents recurrence in refractory ascites, shunt stenosis is common, bypasses liver to reduce pressure on circulation

Question 26

Treatment of encephalopathy

Answer 26

Reversible neuropsychiatric condition- lack of awareness, altered mental state, disorientation, coma Complex aetiology- portosystemic shunting, metabolic dysfunction, alteration of BBB, ammonia heavily implicated Precipitated by GI bleeding, spontaneous bacterial peritonitis, drugs- remove if present

Question 27

Pharmacological treatment of encephalopathy

Answer 27

Lactulose- acidifies colonic contents, leading to ionisation of nitrogenous products and therefore reduction in absorption, 30-40ml/day titrated to achieve 2-3 soft stools per day, causes bloating and diarrhoea Antibiotics- metronidazole reduces ammonia production by GI bacteria

Question 28

Treatment of clotting abnormality

Answer 28

``` Phytomenadione IV (vitamin K)- 10mg daily for 3 days, oral not as effective as IV therefore not used Not effective in patients with significant disease Also avoid NSAIDs, aspirin and anti-coagulants ```

Question 29

Treatment of varices

Answer 29

Shunting of portal blood to systemic circulation- pre-existing vessels dilate, active angiogenesis Initial treatment- stop immediate bleeding, treat hypovolaemic shock, aim to prevent recurrent bleeding

Question 30

Immediate treatment of varices

Answer 30

Terlipressin (vasopressin analogue): systemic vasoconstrictor, infused for 2-5 days

Question 31

Prevention of varices

Answer 31

Band ligation: long term non-selective B blockers e.g. propanolol, decrease PHT by splanchnic vasoconstriction and decrease portal blood flow

Question 32

Acute Liver Failure

Answer 32

Rapid deterioration in liver function in a previously healthy individual, most common cause is a paracetamol overdose Complicated to manage: CNS, CV and renal systems affected, infection and bleeding can be life threatening

Question 33

Paracetamol and the liver

Answer 33

Most common agent of intentional self harm, 20-30 tablets consumed within 24 hours can result in severe hepatocellular necrosis Saturation of glutathione pathway

Question 34

Paracetamol toxicity

Answer 34

0-24 hours: asymptomatic or non-specific signs 24-48 hours: RUQ pain, jaundice, deranged bloods >72 hours: jaundice, somnolence, liver failure Results in: cerebral oedema, shock, sepsis, renal failure

Question 35

Prescribing considerations

Answer 35

Impaired drug metabolism- main route of elimination for many drugs, liver disease must be severe for clinically relevant changes to occur, care with rifampicin and fusidic acid Hypoproteinaemia- albumin produced in the liver, affects highly protein bound drugs Impaired clotting- clotting factors synthesised in the liver, increased sensitivity to oral anticoagulants Hepatic encephalopathy- many drugs can impair cerebral function, care with sedative drugs, opioids, diuretics that decrease K+