WEEK 15 - Jaundice

Question 1

What is the route of transmission for each hepatitis? Is it acute or chronic?

Answer 1

Hep A = faecal-oral, acute

Hep B = blood and bodily fluids, acute and chronic

Hep C = blood and bodily fluids, acute and chronic

Hep D = blood and bodily fluids, acute and chronic (can only be infected if patient also infected with hep B)

Hep E = faecal-oral, chronic (rare and usually associated with immunosuppression)

Question 2

What are 4 essential functions functions of the liver?

Answer 2

1. Destroys or detoxifies harmful endogenous and exogenous substances (eg. Cellular debris, bacteria, drugs)
2. Metabolism of carbs, fats and proteins
3. Produces clotting factors for the clotting cascade
4. Stores excess glucose as glycogen

Question 3

What are the 3 most common causes of liver cirrhosis in the western world?

Answer 3

• non-alcoholic fatty liver disease
• alcohol-related liver disease
• chronic viral hepatitis

Question 4

What is the first serological marker to become positive in a new, acute Hepatitis B infection? Detected on average 4 weeks after exposure to the virus. Usually becomes undetectable after 4-6 months. Detection after 6 months implies chronic hepatitis B infection.

Answer 4

HBsAg

Question 5

The presence of what following acute infection with HBV suggests complete resolution of infection, and is also detectable in those immunised against hep B?

Answer 5

HBsAb or anti-HBs

Question 6

What is present in new acute infection and associated with high Hepatitis B virus DNA levels (HBV DNA)?

Answer 6

HBeAg

Question 7

Patients with high levels of what are more infectious in HBV?

Answer 7

Hepatitis B DNA

Question 8

What appears within weeks of acute infection and remains detectable for 4-8 months?

Answer 8

Hepatitis B core antibody IgM (anti-HBc IgM)

Question 9

What is detectable in virtually all patients exposed to hepatitis B? Can be positive in both acute and chronic infection.

Answer 9

Hepatitis B core Ab IgG (anti-HBc IgG)

Question 10

What features would alert you if hepatotoxicity?

Answer 10

• Confusion due to hepatic encephalopathy
• Liver asterixis (flapping tremor)
• Yellow skin or sclera due to jaundice
• Bruising of the skin or bleeding of the gums or from anywhere due to clotting derangement
• Tenderness in the right upper quadrant due to liver inflammation
• Hepatomegaly

Question 11

What are the initial non-specific usual symptoms in a paracetamol overdose?

Answer 11

• nausea/vomiting
• abdominal pain

Question 12

What are signs and symptoms to be concerned about in a paracetamol overdose?

Answer 12

• acute confusion (encephalopathy)
• reduced urine output
• hypoglycaemia
• reduced consciousness — GCS

Question 13

What is given in paracetamol overdose?

Answer 13

N-Acetylcysteine — it works by acting as a Glutathione donor, preventing toxic build-up of NAPQI

Question 14

When should acetylcysteine treatment be commenced in a paracetamol overdose?

Answer 14

Acetylcysteine treatment should commence in patients:

• whose plasma-paracetamol concentration falls on or above the treatment line on the paracetamol treatment graph
• who present within 8 hours of ingestion of more than 150 mg/kg of paracetamol if there is going to be a delay of 8 hours or more in obtaining the paracetamol concentration after the overdose
• who present 8–24 hours after ingestion of an acute overdose of more than 150 mg/kg of paracetamol even if the plasma-paracetamol concentration is not yet available
• who present more than 24 hours after ingestion of an overdose if they are clearly jaundiced or have hepatic tenderness, their ALT is above the upper limit of normal (patients with chronically elevated ALT should be discussed with the National Poisons Information Service), their INR is greater than 1.3 (in the absence of another cause), or the paracetamol concentration is detectable.

Consider acetylcysteine treatment in patients who present within 24 hours of an overdose if biochemical tests suggest acute liver injury, even if the plasma paracetamol concentration is below the treatment line on the paracetamol treatment graph.

Question 15

Patients who have ingested more than ____ mg/kg of paracetamol in any 24-hour period are at risk of serious toxicity

Answer 15

150

Question 16

When there is uncertainty about whether the presentation was due to therapeutic excess, the patient should be managed as a staggered overdose. What is a staggered overdose?

Answer 16

A staggered overdose involves ingestion of a potentially toxic dose of paracetamol over more than 1 hour, with the possible intention of causing self-harm. All patients who have taken a staggered overdose should be referred to hospital for medical assessment. The MHRA advises that all patients who have ingested a staggered overdose should be treated with acetylcysteine without delay.

Question 17

What is the King’s college criteria for liver transplant following paracetamol overdose?

Answer 17

• arterial pH <7.3 or arterial lactate >3.0 after adequate fluid resuscitation OR
• if all 3 of the following occur in a 24 hour period:
  1. Creatinine >300micromol/l
  2. PT > 100 seconds (INR >6.5)
  3. Grade III/IV encephalopathy

Question 18

When does toxicity from paracetamol overdose peak?

Answer 18

48 to 72 hours after ingestion

Question 19

As the toxicity is from paracetamol metabolites, it is increased in people who have more highly induced ____________ physiology

Answer 19

cytochrome P450

Question 20

How long should you wait to measure paracetamol levels post ingestion?

Answer 20

4 houras

Question 21

What clinical signs and bedside tests would you look for as an indication that the patient is developing liver failure?

Answer 21

• Spontaneous bruising or bleeding at venepuncture sites as a sign of progressive coagulopathy
• Reduced urine output indicating possible acute kidney injury
• Hypoglycaemia (indicated hepatic necrosis)
• Metabolic acidosis despite hydration
• Hypotension despite hydration
• Encephalopathy, which in this case may present with agitation, confusion or aggression rather than drowsiness as seen in chronic liver disease

Question 22

What are potential causes of acute liver failure?

Answer 22

Acute liver failure is rare and can be seen with:

• paracetamol overdose
• severe acute viral hepatitis (help hep E in pregnancy, but also hep A and B) as well as “non-A, non-B hepatitis”
• acute vascular injury to the liver (esp Budd Chiari syndrome)
• autoimmune hepatitis
• direct exposure to toxins such as amanita mushroom poisoning

Question 23

What does a raised ALT suggest?

Answer 23

An inflammatory liver process (ie. A hepatitis). The commonest causes of this could be:

• fatty liver related to alcohol
• a viral infection
• non-alcoholic related fatty liver (usually associated with metabolic syndrome)
• autoimmune liver disease

Much rarer causes would include:
- A1-antitrypsin deficiency
- Wilson’s disease (but this usually presents at a younger age)

Question 24

Full blood count (FBC) - It would be useful to look at the FBC. A mildly raised MCV may suggest underlying ________ while a very high level (greater than 110 fl) is worrying for hazardous alcohol consumption (although ____ and ______ levels would also be necessary in this case). Low platelets would be a concerning feature that she might have _________________ with _____________.

Answer 24

• cirrhosis
• B12 and folate
• portal hypertension with hypersplenism

Question 25

What does HbA1c screen for?

Answer 25

BMI, diabetes and hyperlipidaemia

Metabolic associated fatty liver (previously called non-alcoholic fatty liver – NASH or NAFLD) is associated with metabolic syndrome and thus typically patient might have raised BMI, Hba1c or lipid levels.

Question 26

Prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide is __% in general population and up to __% in patients with type-2 diabetes. A major risk factor is _______.

Answer 26

Prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide is 20% in general population and up to 70% in patients with type-2 diabetes. A major risk factor is obesity.

Question 27

Describe NAFLD

Answer 27

• first stage is hepatic steatosis (fat content >5% of liver volume)
• this progresses to NAFLD where hepatic inflammation develops
• patients with NAFLD are at a higher risk of progression to fibrosis, cirrhosis and hepatocellular carcinoma
• it is usually first detected on routine bloods in asymptomatic individuals
• lifestyle advice and weight loss are the mainstays of treatment alongside reducing/stopping alcohol intake

Question 28

Haemachromatosis is an autosomal ________ genetic condition affecting the ____ gene which causes deficiency of the iron-regulatory hormone ________. Symptoms occur as a result of accumulation of ____ in tissues. Early symptoms include ______, weakness, arthropathy, abdominal pain, _______ dysfunction and cardiac issues (__________ or cardiomyopathy). Late symptoms include: bronzing of the skin, hepatomegaly / cirrhosis of the liver and mood / memory disturbance. The mainstay of treatment is ___________ to lower iron levels in the blood.

Answer 28

Haemachromatosis is an autosomal recessive genetic condition affecting the HFE gene which causes deficiency of the iron-regulatory hormone hepcidin. Symptoms occur as a result of accumulation of iron in tissues. Early symptoms include fatigue, weakness, arthropathy, abdominal pain, erectile dysfunction and cardiac issues (arrhythmia or cardiomyopathy). Late symptoms include: bronzing of the skin, hepatomegaly / cirrhosis of the liver and mood / memory disturbance. The mainstay of treatment is phlebotomy to lower iron levels in the blood.

Question 29

Wilson’s disease is an autosomal ___________ genetic disorder of copper metabolism causing accumulation and toxicity. Hepatic involvement typically presents as _________ hepatitis, cirrhosis or acute liver ________. Neurological and psychiatric symptoms can also occur including tremor, behavioural problems and depression. Low serum ___________ can indicate Wilson’s disease which is a condition treatable with copper chelation agents.

Answer 29

Wilson’s disease is an autosomal recessive genetic disorder of copper metabolism causing accumulation and toxicity. Hepatic involvement typically presents as chronic hepatitis, cirrhosis or acute liver failure. Neurological and psychiatric symptoms can also occur including tremor, behavioural problems and depression. Low serum caeruloplasmin can indicate Wilson’s disease which is a condition treatable with copper chelation agents.

Question 30

What are 90% of hep C cases in UK-born people related to?

Answer 30

Previous recreational drug use

Question 31

Answer 31

No

Question 32

Answer 32

No

The King’s College criteria: liver transplant in paracetamol induced acute liver failure is indicated if:

Arterial pH <7.3 or arterial lactate >3.0 after adequate fluid resuscitation

OR

If all of the three following occur in 24-hour period
- Creatinine >300micromol/l
- PT >100 seconds (INR >6.5)
- Grade III/IV encephalopathy

Question 33

Answer 33

• tattoos and piercings
• IV drug use
• sexual contact
• blood transfusion prior to 1992

Question 34

Answer 34

• liver cirrhosis
• hepatocellular carcinoma
• skin complications eg. Porphyria cutanea tarda
• Sjögren’s syndrome

Question 35

Answer 35

All of the above