Lecture 23

Question 1

Describe Case 1?

Answer 1

• 68yo lady.
• In 1973 had an operation for endometriosis.
• Operation was complicated by peritonitis.
• Further laparotomy; given blood transfusion.
• 8 weeks later - nausea, anorexia, vomiting, looking yellow.
• AST and ALT >1000U/L for 2 weeks; elevated bilirubin for 1 week.
• Admitted to hospital for dehydration (anorexia and vomiting) - given intravenous fluids.
• Symptoms resolved completely after 1 month.

Question 2

Describe the liver test: transaminases?

Answer 2

AST = aspartate transaminase/aminotransferase.
ALT = alanine transaminase/aminotransferase.
When elevated hepatic inflammation, hepatocellular injury.

Question 3

Describe the liver test: GGT and ALP?

Answer 3

GGT = gamma-glutamyl transferase.
ALP = alkaline phosphatase.
When elevated - cholestasis i.e. bile stasis or obstruction.

Question 4

Describe the liver test: Bilirubin?

Answer 4

When elevated causes jaundice (yellow sclera, yellow skin). Can be due to biliary obstruction or hepatocellualr injury.

Question 5

Describe the liver test: albumin and clotting factors?

Answer 5

Produced by liver. When abnormal, suggest impaired synthesis by the liver i.e. the liver is not functioning properly.

Question 6

How do you interpret abnormal liver tests?

Answer 6

1) Recognise a pattern of abnormality. It the pattern of abnormality mostly: hepatocellular (transaminase enzymes significantly elevated more so than the other enzymes), cholestatic (the GGT/ALP predominantly elevated more so than the others) or mixed (both are equally elevated without a preference for one or the other).
2) Is there jaundice. May indicate depending on cholestasis problem or hepatocelular problem a clue of the underlying condition.
3) Is the liver synthetic function impaired? Looks t albumin and prothrombin ratio (measure of clotting time).

Question 7

Describe how the 68yo is in 1993?

Answer 7

Well until 1993. She presents with tiredness, abnormal AST and ALT (200-300 U/L); serum albumin and prothrombin ratio is normal. Tested positive for hepatitis C active infection.

Question 8

What can cause acute hepatitis infection?

Answer 8

Hepatitis B and C.
Acute infection = first 6 months.
Chronic infection = still infected after 6 months.

Question 9

How are Hep B and C transmitted?

Answer 9

Through Blood. Hep B can either be acquired from birth. As an adult Hep B acquired through sexual transmission and injecting drug use. Hep C, the most common way is injecting drug use and blood transfusions.

Question 10

What is Hepatitis C?

Answer 10

RNA single-stranded virus. It was discovered in 1989; diagnostic tests available soon after. It was a cause of post-transfusional hepatitis.

Question 11

What does Hep C exist as?

Answer 11

Many strains known as genotypes. Majority of people infected are unable to eliminate the virus.

Question 12

What are the risk factors for Hep C?

Answer 12

1) Injecting drug use - 60% of cases.
2) Received unscrewing blood products/donated organs: pre-1992 in western countries and in countries with no universal Hep C screening.
3) Sexual: risk is low in monogamous long-term relationships and in absence of HIV.
4) vertical (mother-to-baby): risk also low but can much higher if mother is HIV positive.
5) Occupational.
6) Medical treatments in countries with poor sterile practice.
7) Tattooing or body piercing with non-sterile equipment.

Question 13

Describe the 68yo in 1995?

Answer 13

Decided to have treatment. Was on interferon for 6 months. Had many side affects, treatment failed and remained infected with hepatitis c.

Question 14

Describe Hep C treatment?

Answer 14

For a long time the treatment was based on interferon-drug. Interferon is a cytokine (produced by lymphocytes in response to viral infection - body makes it endogenous). In Hep C treatment patients are given exogenous (additional) interferon to try and increase their immune response against a virus. It causes ‘flu-like’ symptoms (headache, fever, muscle aches and tiredness).

Question 15

How is interferon given?

Answer 15

It is given as a subcutaneous injection i.e. like insulin. For a long time the treatment was a mono-therapy drug. Eventually ribavirin was added. To improve the success rate, interferon was revised to a pegylated form.

Question 16

What is pegylation?

Answer 16

Addition of polyethylene glycol (PEG) molecule to prolong half-life i.e. stays in the body for longer.

Question 17

What are the problems with interferon?

Answer 17

1) Problematic side-effects.
2) Sub-optimal cure rates - with newer regimes, cure rates were better but still only 50-80% depending on genotype.
3) Long duration - 6-12 months depending on genotype.

Question 18

What has occurred in the last few years for Hep C treatment?

Answer 18

Direct-acting antiviral agent drugs have developed. These drugs are taken as tablets, they have better cure rates. The cure rates >90%, and can be achieved without interferon - by just taking a short course of tablets.

Question 19

Describe the 68yo in 1999?

Answer 19

She now has melaena. Passage of black bowel motions which are related to bleeding of upper GI tract. The bleeding is aggressive and life threatening, this is due to the varied under immense pressure and develops portal hypertension.

Question 20

Describe portal circulation?

Answer 20

The vessels that take blood form the entire GI tract and the spleen to the liver. The blood passes through the liver to the inferior vena cava and then back to the heart.

Question 21

Describe portal hypertension?

Answer 21

Pressure in the portal vein is high. It will be difficult for the blood to drain back into the liver. If it occurs over long period of time, the body develops porto-systemic collaterals. These are alternative vessels that divert the blood back from the gut into the right circulation and bypassing the portal vein. They are called varices.

Question 22

Where do varies form?

Answer 22

In the oesophagus and the stomach, and in the mesentery and around the SI.

Question 23

Describe oesophageal and gastric varices?

Answer 23

Present in the oesophagus and the stomach with bleeding. This is due to when the pressure becomes to high, the varices are prone to rupturing and bleeding.

Question 24

Where do varices being?

Answer 24

In the oesophageal junction where they travel upwards as columns of blood vessels. In the fundus of the stomach.

Question 25

What are the causes of portal hypertension?

Answer 25

1) Pre-hepatic: occurring before the liver e.g. portal vein thrombosis.
2) Intra-hepatic: most common cause. Occurs in the liver e.g. cirrhosis, scarring within the liver.
3) Post-hepatic: problem lies beyond the liver, either in the hepatic vein or right sided heart failure.

Question 26

What is the normal portal blood flow?

Answer 26

1000ml/min.

Pressure =

Question 27

What is the portal blood flow in a liver with cirrhosis?

Answer 27

Pressure = >12mmHg, due to stiffness of the liver.

Formation of porto-systemic collaterals i.e. varices.

Question 28

Descrive liver cirrhosis?

Answer 28

Can be caused by anything that leads to chronic injury to the liver. Irreversible scarring of the liver, and indication of advanced disease. Initially the liver enlarges but overtime it progressively shrinks and gets smaller. The surface becomes irregular and nodular.

Question 29

What is fibrosis and cirrhosis of the liver?

Answer 29

Prolonged or repeated liver inflammation i.e. scarring.

Question 30

Is fibrosis reversible?

Answer 30

Potentially if there is allowed time for the liver to regenerate by removing the cause of inflammation. However if there is not enough time, eventually fibrosis becomes irreversible, so there is irreversible scarring = cirrhosis.

Question 31

What happens if cirrhosis progresses?

Answer 31

Initially cirrhosis is mild, so the liver functions normally. However it can progress and eventually the liver can no longer function normally.

Question 32

Describe the 68yo woman in 2001?

Answer 32

She has developed problems with concentration and judgement. She is awake at night and sleeps during the day (naps). Had to stop work and driving was difficult. Confused and disorientated on several occasions. Diagnosed with Hepatic Encephalopathy. She has started taking lactulose, noticed some improvement.

Question 33

What is Hepatic Encephalopathy (HE)?

Answer 33

Result of chronic liver failure. As build up of toxins crossing the blood-brain barrier.

Early symptoms = mood and personality change, inserted sleep pattern (sleep-wake reversal).

Late symptoms = confusion and bizarre behaviour, drowsiness and coma.

Question 34

What is the mechanism of HE?

Answer 34

Liver does not function normally. The liver is unable to detoxify substance produced by bacterial metabolism. In addition, porto-systemic collaterals shunt blood from portal circulation back to the right heart, bypassing the liver. Thus blood is not detoxified by the liver. Then there is a build up of ammonia in the blood. The ammonia passes the blood-brain barrier and disturbs normal brain function.

Question 35

Describe treatment for HE?

Answer 35

Treated with drug called lactulose. It is not the solution to the problem, simply a medication to manage the symptoms. Lactulose is normally used as a laxative. It is a non-absorptive molecule. It decreases ammonia generation by bacteria and converts ammonia to a non-absorbable molecule, thus increasing bowel transit.

Question 36

Describe the 68yo in 2002 and 2003?

Answer 36

She develops abdominal distension. She is diagnosed with ascites and is not responsive to diuretics (tablets to treat fluid overload and ascites). In 2003 she is waitlisted for liver transplantation.

Question 37

What is ascites?

Answer 37

Fluid in the peritoneum causing abdominal distension.

Question 38

What causes ascites?

Answer 38

Portal hypertension. Elevated hydrostatic pressure (exerted by fluid) in portal vein, fluid shifts out of circulation and into the peritoneum. Low oncotic pressure (exerted by proteins) in the portal vein (due to low serum albumin), thus less able to hold onto fluid in circulation.

Question 39

Describe Case 2?

Answer 39

• 41yo woman.

- 10 days of unwell, nausea, anorexia, upper abdominal pain and abdominal distension.

Question 40

Describe the 41yo past medical history?

Answer 40

1) Ulcerative colitis: diagnosed in 1993, prednisone 1-2 months each year, well on no medications for the past 6 months and has occasional loose motions.
2) Asthma.
3) 6 months postpartum, normal delivery. 1 month ago had tubal ligation.

Question 41

Describe the 41yo social and family history?

Answer 41

1) Non-smoker.
2) Nil alcohol.
3) Married with 2 children.
3) Breastfeeding her 6 month year old son.
4) No history of note.

Question 42

Describe the 41yo physical examination?

Answer 42

1) Low grade temperature.
2) Mild jaundice.
3) No signs of chronic liver disease.
4) Grossly distended abdmone with shifting dullness.
5) JVP is normal.
6) Mild ankle oedema.

Question 43

Describe the 41yo blood results?

Answer 43

Bilirubin of 50, AST and ALT are elevated in the 200s. Albumin is low at 30 and clotting is elevated at 1.7.

Question 44

Describe the impression of the 41yo?

Answer 44

Normally well person. Became acutely unwell and developed sudden ascites. Evidence of liver inflammation and jaundice. Blood tests indicate impaired liver function.

Question 45

What is Budd-Chiari syndrome?

Answer 45

It is acute thrombosis of hepatic veins. There is clot in the hepatic veins. The outflow of blood form the liver is obstructed. The liver becomes acutely swollen. You then get acute liver injury (hepatocellular damage). cute portal hypertension can occur, with ascites developing.

Question 46

What does acute portal hypertension in the setting of Budd-Chiari present with?

Answer 46

1) Acute rapidly progressive sever upper abdominal pain.
2) Jaundice.
3) Hepatomegaly.
4) Ascites.
5) Hepatic encephalopathy in fulminant cases - N.B. fulimant is very sever and sudden.

Question 47

What are the causes of Budd-Chiari?

Answer 47

75% - no obvious cause.
25% - cause has been identified.

1) External compression e.g. tumour.
2) Polycythaemia vera - bone marrow makes too many red blood cells.
3) Pregnancy, postpartum.
4) Oral contraceptive pill.
5) Thrombophilia - clotting disorders.
6) Paroxysmal nocturnal haemoglobinuria - genetic mutation where there is a defect in the red blood cel membrane - immune destruction of red blood cells.
7) Hepatocellular carcinoma.

Question 48

How do you manage Budd-Chiari?

Answer 48

Bypass the clot/obstruction. by performing a shunt. A portocaval shunt is a way of diverting th blood flow through the atrial area of obstruction or bypassing the swollen liver. One of the shunts is: Transjugular Intrahepatic Portosystemic Shunt (TIPPS). it is a surgical procedure. It is done with other causes of hypertension. Can try and treat the clot with anticoagulation (i.e. warfarin). Can treat the ascites by giving diuretics.