Liver Disease

Question 1

Is liver small or large

Answer 1

The liver is the largest organ in the body weighing between 1200 and 1500 g in a healthy adult.

Question 2

What cells and structures does the liver consist of?

Answer 2

• Hepatocytes
• Endothelial cells
• Ito cells
• Kuppfer cells
• Central vein
• Portal tract
• And more!

Question 3

Hepatocytes

Answer 3

Hepatocytes make up 80% of the volume of the liver and their primary function is to secrete bile. They are
specialised epithelial cells with 5 to 12 sides and are arranged in complex formations known as hepatic laminae

Question 4

hepatic sinusoids

Answer 4

The hepatic sinusoids are low pressure vascular channels lined with endothelial cells that receive blood from terminal branches of the hepatic artery and portal vein at the periphery of lobules and deliver it into central veins.

The hepatic sinusoids are capillaries found between the rows of hepatocytes. They are highly permeable and
receive oxygenated blood from the hepatic artery and nutrient rich deoxygenated blood from the hepatic portal vein.

Question 5

Bile canaliculi

Answer 5

Bile canaliculi are small ducts that collect bile produced by the hepatocytes. The canaliculi lead into the bile ductules which in turn feed into the bile ducts. The bile ducts eventually merge into the right and left hepatic
ducts which unite and exit the liver as the common hepatic duct.

Question 6

Ito cells

Answer 6

Ito cells are hepatic stellate lipocytes (fat storing cells) that become activated in liver fibrosis due to intoxication (i.e. have a role in hepatic cirrhosis) or hepatotoxic compounds such as carbon tetrachloride.
Their activation is associated with the expression of a sodium/calcium exchanger.

Question 7

The primary functions of the liver are:

Answer 7

Synthesis:
o Plasma protein synthesis (e.g. albumin)
o Synthesis of clotting factors, cholesterol, glucose

Storage
o Storage of glycogen
o Storage and metabolism of fats, carbohydrates, proteins
o Storage of fat soluble vitamins (A,D,E,K) and water soluble vitamin B12

Metabolism
o Detoxification of drugs and other toxins such as ammonia
o Metabolism of hormones (e.g. thyroxine to triiodothyronine, prednisone to prednisolone)

Immunological
o Role of kupffer cells in digesting and removing bacteria, fungi, old blood cells and other foreign materials from blood

Homeostasis
o Maintenance of normal levels of blood glucose

Production of bile
o Formation and secretion of bile (including bilirubin in bile)

Question 8

Acute liver disease

Answer 8

If the onset of a patient’s symptoms occurred within the previous six months, then they are said to have acute
liver disease. Most cases of acute liver disease are self-limiting and consist of damage to or inflammation of
hepatocytes; they tend to resolve without long-term complications.

Question 9

Chronic liver disease

Answer 9

Any patient whose symptoms persist for longer than six months is deemed to have chronic liver disease.
Typically there is longstanding hepatocyte damage resulting in permanent changes to liver structures.

Question 10

Early symptoms of liver disease can include:

Answer 10

• Fatigue
• Loss of appetite
• Weight loss
• Abdominal pain
• Nausea
• Vomiting
• Diarrhoea

Question 11

As the disease progresses symptoms evolve which are more serious in nature:

Answer 11

• Pruritis (caused by hyperbilirubinaemia)
• Jaundice (yellowing of skin and eyes)
• Bruising
• Bleeding from the gut
• Darkened urine
• Swollen ankles
• Swollen abdomen (ascites)

Question 12

Abdominal signs

Answer 12

These include hepatomegaly (an enlarged, palpable liver), ascites and non-specific pain.
Other signs/symptoms which can indicate liver disease include palmar erythema (reddening of palms of hands), spider naevi (small dilated blood vessels near skin surface) and gynaecomastia (enlargement of male
breast tissue).

Question 13

Ascites

Answer 13

This is the accumulation of fluid in the peritoneal cavity as a result of obstruction to blood flow arising from the scarred liver. Additionally, the liver does not produce enough protein resulting in an imbalance of oncotic pressure and a leaking of fluid from the capillary blood vessels into the surrounding tissue. Individuals
presenting with ascites usually have a very swollen abdomen.

Question 14

Spironolactone

Answer 14

an aldosterone antagonist, is licensed for the management of ascites secondary to liver cirrhosis.

Question 15

Spontaneous bacterial peritonitis (SBP)

Answer 15

A complication of ascites in spontaneous bacterial peritonitis (SBP) in which acute bacterial infection occurs in the ascitic fluid. Patients with decompensated liver disease are at the highest risk of this infection. Treatment of SBP is primarily with empiric parenteral antibiotic therapy.

Question 16

Jaundice

Answer 16

Jaundice is also known by the term icterus and can usually be diagnosed from the yellowish tinge that the
unconjugated bile gives to the skin and to the whites of the eyes. Pruritis can be a symptom of jaundice.

Question 17

3 main types of jaundice.

Answer 17

Pre-hepatic jaundice occurs when unconjugated bilirubin is produced by the liver faster than the liver can conjugate it.

Hepatic jaundice occurs when the liver cells are damaged by viral hepatitis, alcoholic cirrhosis, drug-induced jaundice, alcoholic hepatitis or primary biliary cirrhosis.

Posthepatic jaundice generally occurs when there is obstruction of the bile duct by gall stones.

Question 18

Propranolol

Answer 18

A beta blocker metabolised by the liver, is a first line treatment for the management of portal hypertension. The BNF states that it is licensed for the prophylaxis of variceal bleeding in portal hypertension.

Question 19

Coagulopathy treatment

Answer 19

Treatment includes endoscopic banding, injection sclerotherapy and the use of drugs such as terlipressin to stop the bleeding.

Question 20

Hepatitis

Answer 20

This is inflammation of the liver and may have many causes. It is important to identify and address the underlying cause since inflammation may progress to fibrosis, scarring, cirrhosis or ultimately cancer.
Conditions causing hepatitis are discussed later.

Question 21

Cirrhosis

Answer 21

Cirrhosis is the result of long term damage to the liver and arises when healthy liver tissue becomes replaced by nodular and scarred (fibrotic) tissue over time. It can occur without the individual noticing any symptoms.
The scarred tissue impedes normal blood flow in the liver leading to reduced and eventual loss of function. It is usually irreversible in its later stages.

Question 22

Wernicke-Korsakoff’s syndrome

Answer 22

This entails two separate conditions which may occur at the same time and are both linked to thiamine deficiency. Korsakoff’s psychosis or syndrome usually develops after Wernicke’s encephalopathy has already developed and its symptoms have subsided. Korsakoff’s psychosis arises from permanent brain damage.
Management is aimed at preventing or limiting the syndrome.

Question 23

Compensated liver disease

Answer 23

This can be described in chronic liver disease in which there are little or no symptoms of the disease and the liver is still adequately functional.

Question 24

Decompensated liver disease

Answer 24

This occurs in chronic liver disease where the liver is no longer able to carry out normal functioning resulting in the sudden development of symptoms. The complications which arise can include fluid retention and encephalopathy.

Question 25

causes of liver disorders

Answer 25

• Viral infection
• Alcohol misuse
• Metabolic disorder including insulin resistance
• Immune disorders
• Genetic conditions
• Drugs
• Obstructive jaundice
• Malignancy

Question 26

Viral hepatitis

Answer 26

The main viruses (hepatitis A, B and C) associated with hepatic disease are described in Table 1 below.
Hepatitis D and E viruses are also associated with liver disease.

Question 27

Virus type, cause and

disease durations - HEP A

Answer 27

Hepatitis A (HAV)
Cause: Ingestion of contaminated water and food via the ‘faecal-oral route’, direct contact with an infectious person.
Duration: Acute however recovery can take weeks or months. Does not cause chronic liver disease and is rarely fatal.

Question 28

Symptoms - HEP A

Answer 28

Incubation 14-28 days.
Symptoms range from mild to severe (e.g. fever, nausea, diarrhoea, loss of appetite, dark urine, jaundice). Usually selflimiting.

Question 29

Management, prevention and treatment - HEP A

Answer 29

Management is conservative. Once recovered, patients no longer carry the virus. Avoid paracetamol and antiemetics to treat symptoms. Best management is primary prevention by improved sanitation, food safety and vaccination.

Question 30

Virus type, cause and

disease durations - HEP B

Answer 30

Hepatitis B (HBV)
Cause: Transmission via contact with blood or other body fluids of an infected individual.
Duration: Acute and chronic. Attacks the liver and is potentially lifethreatening.

Question 31

Symptoms - HEP B

Answer 31

Average incubation time is 75 days (varies from 30-180 days).
The virus can survive outside the body for up to 7 days.
Usually symptom-free during acute phase infection however some may have symptoms (as described above). High risk of death from cirrhosis and liver cancer. Diagnosis involves detection of Hepatitis B surface antigen (HBsAg).

Question 32

Management, prevention and treatment - HEP B

Answer 32

Management includes nutritional support and maintaining fluid balance. Chronic hepatitis can be treated with peginterferon alpha-2a and antivirals such as tenofovir or entecavir. They can slow disease progression of cirrhosis and liver cancer. Primary prevention is by vaccination, especially for those in high risk groups, e.g. sex workers, IV drug users and healthcare professionals at risk of hepatitis B exposure.

Question 33

Virus type, cause and

disease durations - HEP C

Answer 33

Cause: Transmitted via exposure to blood. 70% of patients are IV drug users.
Duration: Acute and chronic. Rarely lifethreatening.

Question 34

Symptoms - HEP C

Answer 34

Incubation 2 weeks to 6 months.
Usually asymptomatic.
If symptoms appear they include those described as for HAV and HBV. The disease can slowly progress, taking about 20 years from infection to cirrhosis.
Approx. 15-45% of patients clear the virus within 6 months without treatment. Remaining individuals develop chronic infection.

Question 35

Management, prevention and treatment - HEP C

Answer 35

Treatment is not always needed.
Treatment choice depends on genotype and viral load. Pegylated interferon/ribavirin combination is used for chronic hepatitis C. WHO recommends Sofosbuvir, daclatasvir and the sofosbuvir/ledipasvir combination are part of preferred regimens which can achieve cure rates above 95%. They are considered safer, more effective and better tolerated compared to the older therapies. An HCV vaccine is not available therefore reducing risk of exposure is the primary goal.

Question 36

Alcoholic liver disease (ALD)

Answer 36

Alcohol related liver disease is the most common cause of liver injury in the UK and is still rising.
ALD accounts for 37% of all deaths caused by liver disease. It is a preventable condition.
Factors such as age, genetics, and gender play a part including co-existing conditions such as diabetes, viral infection and metabolic syndrome.
The risk of developing ALD rises with increasing daily alcohol consumption and the period of time in years over which an individual drinks. ALD has three stages: fatty liver, alcoholic hepatitis, and cirrhosis. Individuals who misuse alcohol may damage their liver over time without experiencing symptoms. By the time ALD is diagnosed significant liver damage may have already developed.
Diagnosis includes taking a detailed history of alcohol consumption and patterns, undertaking a
physical examination and measuring biochemical markers including liver function tests (LFTs).
Scanning and liver biopsy can provide additional information. A raised gamma-glutamyl transferase (GGT) is usually indicative of excessive alcohol intake.
Management strategies for alcohol dependence include psychosocial, behavioural and pharmacological treatments. Abstinence is the best strategy to halt the progression of liver damage.
Drug therapy is aimed at managing specific features of alcohol misuse. Individuals exhibiting alcohol withdrawal have symptoms which may include tremor, sweating, anxiety, weakness, GI symptoms, hallucinations and seizures. The main class of drugs used to manage withdrawal symptoms are the benzodiazepines, for example, chlordiazepoxide, diazepam and lorazepam
are commonly used drugs. Patients who are admitted to hospital are prescribed reducing courses of oral benzodiazepines using local treatment protocols. The antiepileptic action of benzodiazepines also serves to treat or prevent alcohol-related withdrawal seizures. Vitamin B deficiency is common in ALD and patients are at risk of developing Wernicke’s encephalopathy,
caused by thiamine (vitamin B1) deficiency. A course of parenteral thiamine is given for those at high risk and is followed by oral therapy.

Question 37

Prevention of relapse of alcohol misuse

Answer 37

Acamprosate and naltrexone are two agents which may be used to treat relapse prevention.

Disulfiram is now used only where acamprosate and naltrexone are not suitable. Acamprosate and naltrexone are effective in reducing cravings and maintaining abstinence in alcohol dependent patients. The drugs are usually prescribed under specialist care as soon as
abstinence has been achieved. Drug treatment is stopped if regular drinking is resumed and continued for 4-6 weeks.

Disulfiram causes a very unpleasant reaction if the individual drinks even very small quantities of alcohol. The reaction is thought to be due to build-up of acetaldehyde. Symptoms include flushing, headache, palpitations, nausea and vomiting. Intake of larger quantities of alcohol can cause more serious symptoms such as arrhythmias, hypotension and collapse.

Nalmefene, licensed for reduction of alcohol reduction, is prescribed for patients with a high risk drinking level who do not have withdrawal symptoms and do not require immediate detoxification.

Question 38

Non-alcoholic related fatty liver disease (NAFLD)

Answer 38

This condition is caused by a build-up of excess fats (triglycerides) in the liver in individuals who do not exceed the recommended safe drinking limits. NAFLD appears to be increasing in incidence. Those most at risk of developing the condition are usually aged around 50 years, are overweight, eat a poor diet, take little exercise and have metabolic syndrome. Metabolic syndrome is a condition characterised by insulin resistance, type 2 diabetes, hypertension, raised triglycerides and large waist circumference.

Question 39

Immune disorders

Answer 39

Autoimmune diseases are uncommon. If they do occur the signs and symptoms include fatigue, right upper quadrant pain, polymyalgia/arthralgia, abnormal LFTs. Treatment includes initial drug therapy with corticosteroids followed by azathioprine treatment (used as a steroidsparing
drug).
Primary biliary cirrhosis (PBC) or primary biliary cholangitis is a relatively common cause of liver disease associated with chronic cholestasis and is thought to have a genetic predisposition. It appears to be immunologically mediated. It is a form of cholestatic jaundice (post-hepatic obstructive jaundice) in which there is destruction of intra-hepatic bile ducts. Symptoms include fatigue and pruritis, with jaundice developing in advanced disease. Liver function tests show a raised gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP).
Ursodeoxycholic acid will slow progression of the disease but transplantation is required in advanced cases.

Question 40

Genetic conditions

Answer 40

These include haemochromatosis which is iron overload resulting in cirrhosis and diabetes.
Wilson’s disease is an inherited disorder in which excessive copper is deposited in the hepatocytes

Question 41

Drug induced liver disease.

Answer 41

A number of drugs have been associated with liver toxicity. Examples include analgesics (most notably paracetamol), anticonvulsants, statins, anti-tubercular agents, methotrexate and amiodarone. Mechanisms are described as immune-mediated or idiosyncratic in nature.
Symptoms are similar to those for acute viral hepatitis. Management involves identifying and discontinuing the offending drug where possible. Drugs known to be associated with liver toxicity should not be initiated in patients with liver disease.

Question 42

Obstructive jaundice

Answer 42

This is also known as cholestatic liver disease and occurs when bile flow excreted from the liver is reduced or blocked. The result is a raised level of bilirubin in the blood. The condition can develop from a range of causes such as gall stones (which block the bile duct), drugs, ALD, or tumours of the bile duct, liver or pancreas. Symptoms include pruritis, fatigue and jaundice.
Management is aimed at identifying and treating, if possible, the exact underlying cause.

Question 43

Malignancy

Answer 43

Two types of liver cancer are described: primary and secondary. Primary liver cancer commonly arises from liver cirrhosis as a result of viral hepatitis, excess alcohol, NAFLD and haemochromatosis.
Secondary liver cancer results from migration of cancerous cells to the liver from a primary
tumour elsewhere in the body. It is commonly associated with cancers of the colon, stomach, pancreas, lung and breast.

Question 44

Diagnosis of liver disease

Answer 44

A full medical history and physical examination should provide a good indication of the presence of liver disease including observation of signs such as an inflamed or enlarged liver and the presence of jaundice. Diagnosis will also involve a range of blood tests including liver function test (LFTs).
Ultrasound or MRI scanning is used to provide an image of the liver and its structure. Presence of a fatty liver, ascitic fluid, tumours, cysts, and dilated extrahepatic ducts can be identified via scans. A liver biopsy may be taken to determine an underlying cause and the extent of liver damage, for example the presence and extent of fibrosis in the tissue.

Question 45

Liver function tests (LFTs)

Answer 45

Analysing blood tests for a number of enzymes and substances associated with liver function can indicate inflammation and damage to the liver. The tests can also indicate the presence of biliary tract disease. The extent to which LFTs are raised does not necessarily translate into degree of liver damage or functional capacity.
Abnormal tests do not exclusively point to liver disease since they can be raised in other extrahepatic conditions. Also, normal test results can be found in patients with severe liver disease.
Patterns of raised enzymes can give an indication of probable cause of liver injury, for example, an AST: ALT ratio of 2:1 times or greater may indicate alcohol-related liver disease. Therefore it is important to look at the trends in LFT values. An increase in transaminases by greater than double the upper limit of normal is considered to be of significance in determining a problem
with the liver.
LFT measurements usually include all of the following:
• Alanine aminotransferase (ALT)
• Aspartate aminotransferase (AST)
• Bilirubin (conjugated and total bilirubin tests)
• Gamma-glutamyl transferase (GGT)
• Alkaline phosphatase (ALP)
• Albumin
• Lactate dehydrogenase (LDH)

Question 46

Scoring systems used in chronic liver disease

Answer 46

These include the Child-Pugh classification and the Model for end-stage liver disease (MELD).
The Child-Pugh classification assesses five variables; ascites, encephalopathy, serum albumin, bilirubin and INR. Scores from A (least severe) to C (most severe) determine disease severity.
MELD stratifies the severity of end-stage liver disease in order to prioritise patients for transplant.

Question 47

Drug metabolism in the liver Phase I

Answer 47

Metabolism is mediated by cytochrome p450 and results in oxidation, reduction and hydrolysis of drug molecules. The metabolites are more water soluble and are often active and toxic to the body

Question 48

Drug metabolism in the liver Phase II

Answer 48

The metabolites are conjugated with polar groups rendering the metabolites inactive. These are then excreted via the bile or the urine.
• There is an altered first pass metabolism effect due to the development of shunts (extrahepatic blood vessels).
• Albumin production decreases in liver disease which affects those drugs that are extensively protein bound (thus necessitating dose reduction).
• The development of ascites increases the volume of distribution of hydrophilic drugs.
• The destruction of or damage to liver cells results in reduced metabolising enzyme production.
• There are extra-hepatic effects to consider e.g. increased CNS sensitivity to opioids, Increased renal sensitivity to NSAIDs.

A number of factors should be considered when prescribing drugs in liver disease:
o The patient’s signs and symptoms
o Liver function test values and prothrombin time (PT)/INR values
o Albumin levels
o Other related investigations e.g. ultrasound scan
o Properties of the drug being considered (metabolism, pharmacokinetics, potential side effects)

Question 49

What is first pass metabolism?

Answer 49

Drugs are absorbed by the GI tract, carried to the liver via the portal vein where they undergo usually significant metabolism.
Subsequently only a proportion of the drug reaches the circulation and the site of action. The liver is the major site of first pass metabolism but other sites include the GI tract.

Question 50

How may first pass metabolism be bypassed?

Answer 50

Use alternate routes of administration such as buccal, sublingual, parenteral

Question 51

a) What advice should a patient with ascites be offered regarding sodium and the diet?
b) Which medications should be avoided in this patient?

Answer 51

Restrict sodium in the diet in order that ascites/fluid retention is not made worse.
Medication to avoid include effervescent tablets, sodium containing liquids

Question 52

Pruritis

a) Why may patients who have liver disease experience pruritis?
b) What medication can be offered to a patient for the management of pruritis?

Answer 52

Hyperbilirubinameia predisposes to jaundice and pruritis. Bile sequestering agents such as colestyramine are used for pruritis secondary to biliary disease. Ursodeoxycholic acid is licensed for PBC. Others found in the literature include rifampicin, naltrexone, antihistamines. In clinical practice antihistamines have not found to work well.

Question 53

Drugs to be used with caution or avoided in liver disease - a) A patient who has had a seizure from alcohol withdrawal

Answer 53

e.g. quinolone antibiotics, tramadol

Question 54

Drugs to be used with caution or avoided in liver disease - b) A patient with liver ascites

Answer 54

e.g. Diuretics, drugs which contain sodium or promote retention of sodium

Question 55

Drugs to be used with caution or avoided in liver disease - c) A patient with liver disease and an albumin level of 29g/L.

Answer 55

e.g. any drug transported in the blood on albumin such as phenytoin

Question 56

Drugs to be used with caution or avoided in liver disease - d) A patient with an INR of 1.9 and a prothrombin time (PT) time of 18 seconds

Answer 56

e.g any drug which may cause bleeding such as NSAIDS, antiplatelets, heparins

Question 57

Drugs to be used with caution or avoided in liver disease - e) A patient with abnormally raised LFTs and newly diagnosed with rheumatoid arthritis

Answer 57

e.g methotrexate

Question 58

Drugs to be used with caution or avoided in liver disease - f) A patient with pre-existing liver disease requiring treatment for tb

Answer 58

e.g Rifampicin

Question 59

a) Which class of drugs is used to management alcohol withdrawal features such as shakiness, tremors, sweating and anxiety?

Answer 59

benzodiazepines

Question 60

Case 1
A 19 year old patient with severe learning difficulties is admitted to A & E for management of a medication overdose. The patient found some Anadin Extra tablets in the home and has taken 24 tablets over a 24 hour period. The Registrar contacts the community pharmacist to ask what is in the tablets. Current medication history:
o Co-codamol soluble tablets 8/500 1-2 QDS for pain relief
o Amoxicillin 250mg in 5ml oral suspension, 500mg three times daily for 5 days for otitis media.

1. What are the risks associated with this medication overdose and why is the drug
   history important?
2. What is the likely management of the medication overdose for this patient?

Answer 60

• Paracetamol contained in Anadin extra and co-codamol which carries high risk of liver damage and fulminant liver failure if taken in overdose
• Prompt use of the antidote acetylcysteine dosed according to amount of paracetamol ingested.

Question 61

Case 2
A 28 year old unemployed man has been asked to see his GP following the results of a blood test. He currently takes methadone 1mg per ml oral solution at a dose of 20mg once daily and receives supervised administration from his community pharmacist. The patient is
asymptomatic.
AST 200IU/L
ALT 198IU/L
ALP 40IU/L
GGT 60IU/L
ALBUMIN 40G/L
TOTAL BILIRUBIN 10micromol/L

1. What explanation can be offered for the blood test results? Justify your answer.

Answer 61

Transaminases and GGT are raised indicating liver disease. He is asymptomatic which may be a feature of viral hepatitis. He is taking methadone to manage drug addiction.
Likelihood he has been or is an IVDU and therefore there are risks associated with contracting hepatitis C infection. Patient will require further tests to confirm presence of
Hepatitis C (or other virus).

Question 62

Case 3
A 45 year old airline pilot has been admitted to hospital with abdominal pain, vomiting and
shakiness. On examination he has abdominal tenderness, is sweaty and has some bruising to his arms and legs. Following admission the patient has a bout of haematemesis

AST 35IU/L
ALT 32IU/L
ALP 63IU/L
GGT 143IU/L
ALBUMIN 31G/L
TOTAL BILIRUBIN 10micromol/L
PROTHROMBIN TIME 19 seconds

1. What is the most likely cause of the symptoms and blood results?
2. What drug therapy may be used to manage the patient’s haematemesis?
3. What other acute drug therapy would you recommend for this patient and why?

Answer 62

1. Likely cause of symptoms is alcohol withdrawal symptoms. GGT is raised which is highly indicative of alcohol misuse. Albumin is low and PT is raised suggesting the liver’s synthesis ability is impaired. The patient is likely to have liver damage (alcoholic hepatitis).
2. Terlipressin is licensed to treat bleeding varices. Surgical banding and sclerotherapy may be used.
3. The patient should receive a course of a benzodiazepine such as chlordiazepoxide for
   withdrawal symptoms and should also have parenteral thiamine injection to prevent development of Wernicke’s encephalopathy

Question 63

Case 4
A 65 year old woman is admitted to hospital with icterus, itchiness and lethargy. The medical notes report discoloured urine. Medication history includes co-amoxiclav 625mg three times daily for 14 days.

AST 56IU/L
ALT 60IU/L
ALP 38IU/L
GGT 28IU/L
ALBUMIN 40G/L
TOTAL BILIRUBIN 35micromol/L

1. What is the most likely cause of the symptoms and the blood results?
2. What management would you advise?

Answer 63

1. Symptoms suggestive of jaundice. Transaminases only slightly raised but bilirubin is quite raised. Other enzymes and albumin are in normal range. Given the co-amoxiclav for the length of course received this patient is likely to have cholestatic jaundice as a side effect of the antibiotic
2. Stop co-amoxiclav immediately and seek specialist advice. An alternate antibiotic may be required which does not cause liver side effects

Question 64

Case 5
A 60 year old woman has had a blood test on the 1.5.17 and attends a GP appointment the
following day to receive the results. Medication history as follows:
Simvastatin 40mg at night started on 1.2.17
Amlodipine 10mg once daily started on 1.4.17

AST 20IU/L 200IU/L
ALT 22IU/L 225IU/L
ALP 12IU/L 12IU/L
GGT 30IU/L 29IU/L
ALBUMIN 40G/L 40G/L
TOTAL BILIRUBIN 13micromol/L 13micromol/L

1. What is/are the cause(s) of the change in the LFT readings?
2. What management would you recommend to the GP?

Answer 64

1. Statin therapy. Transaminases are raised by >10 times the normal range
2. Stop statin therapy and review patient. R/V diet for cholesterol management.

Question 65

fulminant hepatitis describes

Answer 65

• Acute liver failure (often due to paracetamol overdose).
• Patient presents with jaundice followed by encephalopathy.
• Prompt liver transplantation needed.

Question 66

Some examples of drugs with high hepatic extraction

Answer 66

Antidepressants
Chlorpromazine/haloperidol
Calcium channel blockers
Morphine
Glyceryl trinitrates
Levodopa
Propranolol

Question 67

Some examples of drugs with low hepatic extraction

Answer 67

NSAIDs
Diazepam
Carbamazepine
Phenytoin
Warfarin

Question 68

Hepatorenal syndrome

Answer 68

This syndrome usually occurs when there is advanced cirrhosis and ascites present. Oliguria and azotaemia
develop in the presence of structurally normal kidneys

Question 69

hepatic laminae

Answer 69

hepatic laminae – basically plates of hepatocytes one cell thick. These laminae are bordered by hepatic sinusoids. Grooves in the cell membranes provide spaces for the canaliculi.

Question 70

Kuppfer cells

Answer 70

Kuppfer cells are stellate reticuloendothelial cells located in the hepatic sinusoids. Their function is to destroy old white and red blood cells, bacteria and foreign matter in venous blood from the GI tract.

Question 71

Portal Hypertension

Answer 71

The portal vein carries approximately 1500 mL/min of blood from the small and large bowel, the spleen and
the stomach to the liver at a pressure of 5 to 10 mmHg. Obstruction of this flow or increased resistance to the
flow results in portal hypertension. The most common causes are alcoholic cirrhosis and viral cirrhosis in
Western countries, schistosomiasis (infection caused by a parasitic worm) in developing countries and portal
vein thrombosis in children.
The obstruction to the blood flow in the portal vein leads to development of collateral blood vessels elsewhere, most commonly in the upper part of the GI tract. These new blood vessels are very fragile and break and bleed easily resulting in bleeding varices, a very serious condition (see under coagulopathy). Also, because the blood supply is diverted from the liver there may be accumulation of toxins in the abdomen which results in the development of ascites.

Question 72

Coagulopathy

Answer 72

The liver is responsible for synthesis of most clotting factors and other proteins concerned with blood
homeostasis. Abnormalities of coagulation can occur in liver disease often manifested as bruising and prolonged bleeding times. A prolonged prothrombin time (PT), raised INR and altered platelet count can indicate a problem with the liver’s normal clotting processes. More serious consequences include the development of varices which occur in the oesophagus or stomach.
They are dilated blood vessels which result from a sustained portal hypertension (see above). Variceal bleeding is life threatening and requires urgent medical attention.

Question 73

c) Why are patients only given a short reducing course of treatment in hospital but NOT prescribed these drugs on discharge from hospital?

Answer 73

Risk of patient resuming drinking while taking BZPs is dangerous – increased sedative effect leading to falls and injury especially if patient has raised PT/INR (bleeding risk).

Question 74

b) What properties do these drugs possess which make them suitable for management
of withdrawal symptoms?

Answer 74

Anxiolytics, muscle relaxants, anti-seizure properties

Question 75

examples of drugs which undergo first pass metabolism?

Answer 75

Propranolol, GTN, amlodipine

Question 76

Hepatic encephalopathy

Answer 76

This condition is caused by a build-up of toxic products (including ammonia) in the blood stream which the severely damaged liver cannot remove. Toxins results in deterioration of brain function leading to confusion,
drowsiness, and mood and personality changes. On physical examination the individual may demonstrate a
flapping motion of the hands when the arms are outstretched. This is called asterixis.

Hepatic encephalopathy in an individual with long standing liver disease may also be triggered by certain
events such as an infection, dehydration, electrolyte imbalance, a GI bleed, by not taking drugs as prescribed
or by taking certain drugs such as analgesics or diuretics.

Question 77

Hepatic encephalopathy management

Answer 77

Management is aimed at identifying and removing the precipitating cause where possible. If the patient is on
diuretics these are stopped and the patient’s electrolytes are closely monitored. The patient is rehydrated and a careful watch on fluid balance is maintained.
Restricting dietary protein (breakdown to ammonia products) and use of lactulose to limit absorption of
ammonia products from the gut can treat the condition.

Rifaximin, an antibiotic not absorbed by the gut, is used to reduce the number of bacteria producing toxins
from the digestive tract. Rifaximin is licensed for the management of reduction in recurrence of hepatic
encephalopathy

Question 78

Wernicke’s encephalopathy

Answer 78

This results from thiamine (vitamin B1) deficiency as a result of alcohol misuse. Symptoms are as for hepatic encephalopathy and may initially be confused with intoxication in an individual

Question 79

Paracetamol

Answer 79

Paracetamol is a drug predictably known to cause fatal liver injury when taken in overdose. It is usually metabolised by a saturable enzyme pathway producing non-toxic metabolites. However in paracetamol overdose, another metabolic pathway is used which produces a toxic metabolite N-acetyl-para-benzoquinoneimine (NAPQI) causing acute liver injury and risk of death. Emergency treatment as soon as possible after overdose with acetylcysteine infusion is required

Question 80

a) Which medication may be used to manage hepatic encephalopathy?
b) Which medication should be avoided in hepatic encephalopathy?

Answer 80

Rifaximin is used to manage a reduction in recurrence of hepatic encephalopathy. Lactulose is also used for the condition usually in higher doses than used for constipation.
Medication to avoid include drugs affecting the CNS and causing sedation e.g. opioids, benzodiazepines, any other drugs with sedative properties. Also avoid drugs which predispose to bleeding risks such as NSAIDs (think variceal risk).

Question 81

Complication of portal hypertension

Answer 81

The major potentially life threatening complication of portal hypertension is torrential venous heamorrhage (variceal bleed) from the thin walled veins in the oesophagus and upper stomach.

Question 82

Treatment for autoimmune hepatitis

Answer 82

Corticosteroids, azathioprine

Question 83

Treatment for wilsons disease

Answer 83

Chelation therapy - penicillamine