Chronic Liver Disease

Question 1

Describe Cirrhosis

Answer 1

Liver cirrhosis is the result of chronic inflammation and damage to liver cells. When the liver cells are damaged they are replaced with scar tissue (fibrosis) and nodules of scar tissue form within the liver. This fibrosis affects the structure and blood flow through the liver, which causes increased resistance in the vessels leading in to the liver. This is called portal hypertension.

Question 2

Most common causes of liver cirrhosis?

Answer 2

Alcoholic liver disease
Non Alcoholic Fatty Liver Disease
Hepatitis B
Hepatitis C

Question 3

Rarer causes

Answer 3

Autoimmune hepatitis
Primary biliary cirrhosis
Haemochromatosis
Wilsons Disease
Alpha-1 antitrypsin deficiency
Cystic fibrosis
Drugs (e.g. amiodarone, methotrexate, sodium valproate)

Question 4

Signs of cirrhosis

Answer 4

Jaundice – caused by raised bilirubin
Hepatomegaly – however the liver can shrink as it becomes more cirrhotic
Splenomegaly – due to portal hypertension
Spider Naevi – these are telangiectasia with a central arteriole and small vessels radiating away
Palmar Erythema – caused by hyperdynamic cirulation
Gynaecomastia and testicular atrophy in males due to endocrine dysfunction
Bruising – due to abnormal clotting
Ascites
Caput Medusae – distended paraumbilical veins due to portal hypertension
Asterixis – “flapping tremor” in decompensated liver disease

Question 5

Liver biochemistry results

Answer 5

Liver biochemistry is often normal, however in decompensated cirrhosis all of the markers (ALT, AST, ALP and bilirubin) become deranged.

Question 6

Albumin and prothrombin

Answer 6

Albumin and prothrombin time are useful markers of the “synthetic function” of the liver. The albumin level drops and the prothrombin time increases as the synthetic function becomes worse.

Question 7

what does hyponatraemia indicate?

Answer 7

Hyponatraemia indicates fluid retention in severe liver disease.

Question 8

Urea and Cr

Answer 8

Urea and creatinine become deranged in hepatorenal syndrome.

Question 9

What is alpha-fetoprotein and when is it tested?

Answer 9

Alpha-fetoprotein is a tumour marker for hepatocellular carcinoma and can be checked every 6 months as a screening test in patients with cirrhosis along with ultrasound.

Question 10

Ultrasound in cirrhosis

Answer 10

Nodularity of the surface of the liver
A “corkscrew” appearance to the arteries with increased flow as they compensate for reduced portal flow
Enlarged portal vein with reduced flow
Ascites
Splenomegaly
Ultrasound is also used as a screening tool for hepatocellular carcinoma. NICE recommend screening patients with cirrhosis for HCC every 6 months.

Question 11

Fibroscan

Answer 11

“FibroScan” can be used to check the elasticity of the liver by sending high frequency sound waves into the liver. It helps assess the degree of cirrhosis. This is called “transient elastography” and should be used to test for cirrhosis. NICE recommend retesting every 2 years in patients at risk of cirrhosis:

Hepatitis C
Heavy alcohol drinkers (men drinking > 50 units or women drinking > 35 units per week)
Diagnosed alcoholic liver disease
Non alcoholic fatty liver disease and evidence of fibrosis on the ELF blood test
Chronic hepatitis B (although they suggest yearly for hep B)

Question 12

endoscopy

Answer 12

Endoscopy can be used to assess for and treat oesophageal varices when portal hypertension is suspected.

Question 13

CT and MRI

Answer 13

CT and MRI can be used to look for hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes and ascites.

Question 14

Liver biopsy

Answer 14

Liver biopsy can be used to confirm the diagnosis of cirrhosis.

Question 15

What makes up the child-pugh score?

Answer 15

Bilirubin
<34
34-50
>50

Albumin
>35
28-35
<28

INR
<1.7
1.7-2.3
>2.3

Ascites
None
Mild
Moderate or severe

Encephalopathy
None
Mild
Moderate or severe

Question 16

MELD score

Answer 16

The MELD score is recommended by NICE to be used every 6 months in patients with compensated cirrhosis. It is a formula that takes into account the bilirubin, creatinine, INR and sodium and whether they are requiring dialysis. It gives a percentage estimated 3 month mortality and helps guide referral for liver transplant.

Question 17

Management

Answer 17

Ultrasound and alpha-fetoprotein every 6 months for hepatocellular carcinoma
Endoscopy every 3 years in patients without known varices
High protein, low sodium diet
MELD score every 6 months
Consideration of a liver transplant
Managing complications as below

Question 18

Complications of cirrhosis

Answer 18

Malnutrition
Portal Hypertension, Varices and Variceal Bleeding
Ascites and Spontaneous Bacterial Peritonitis (SBP)
Hepato-renal Syndrome
Hepatic Encephalopathy
Hepatocellular Carcinoma

Question 19

Malnutrition in cirrhosis

Answer 19

Cirrhosis leads to malnutrition and muscle wasting. A simplified explanation of this is that it leads to increased use of muscle tissue as fuel and reduces the protein available in the body for muscle growth. Cirrhosis affects the metabolism of proteins in the liver and reduces the amount of protein produced. It also disrupts the livers ability to store glucose as glycogen and release it when required. This results in the body using muscle tissue as fuel leading to muscle wasting and weight loss.

Question 20

managing malnutrition

Answer 20

Regular meals (every 2-3 hours)
Low sodium (to minimise fluid retention)
High protein and high calorie (particularly if underweight)
Avoid alcohol

Question 21

Ascites

Answer 21

Ascites is basically fluid in the peritoneal cavity. The increased pressure in the portal system causes fluid to leak out of the capillaries in the liver and bowel and in to the peritoneal cavity. The drop in circulating volume caused by fluid loss into the peritoneal space causes a reduction in blood pressure entering the kidneys. The kidneys sense this lower pressure and release renin, which leads to increased aldosterone secretion (via the renin-angiotensin-aldosterone system) and reabsorption of fluid and sodium in the kidneys.

Question 22

What kind of ascites does cirrhosis cause?

Answer 22

Cirrhosis causes a transudative, meaning low protein content, ascites.

Question 23

Managing ascites

Answer 23

Low sodium diet
Anti-aldosterone diuretics (spironolactone)
Paracentesis (ascitic tap or ascitic drain)
Prophylactic antibiotics against spontaneous bacterial peritonitis (ciprofloxacin or norfloxacin) in patients with less than 15g/litre of protein in the ascitic fluid
Consider TIPS procedure in refractory ascites
Consider transplantation in refractory ascites

Question 24

What is SBP?

Answer 24

Spontaneous Bacterial Peritonitis (SBP)
This occurs in around 10% of patients with ascites secondary to cirrhosis and can have a mortality of 10-20%. It involves an infection developing in the ascitic fluid and peritoneal lining without any clear cause (e.g. not secondary to an ascitic drain or bowel perforation).

Question 25

How does SBP present?

Answer 25

Can be asymptomatic so have a low threshold for ascitic fluid culture
Fever
Abdominal pain
Deranged bloods (raised WBC, CRP, creatinine or metabolic acidosis)
Ileus
Hypotension

Question 26

How does SBP present?

Answer 26

Can be asymptomatic so have a low threshold for ascitic fluid culture
Fever
Abdominal pain
Deranged bloods (raised WBC, CRP, creatinine or metabolic acidosis)
Ileus
Hypotension

Question 27

most common organisms in SBP?

Answer 27

Escherichia coli
Klebsiella pnuemoniae
Gram positive cocci (such as staphylococcus and enterococcus)

Question 28

managing SBP

Answer 28

Take an ascitic culture prior to giving antibiotics

Usually treated with an IV cephalosporin such as cefotaxime

Question 29

What is hepatorenal syndrome?

Answer 29

Hepatorenal syndrome occurs in liver cirrhosis. Hypertension in the portal system leads to dilation of the portal blood vessels, stretched by large amounts of blood pooling there. This leads to a loss of blood volume in other areas of the circulation, including the kidneys. This leads hypotension in the kidney and activation of the renin-angiotensin system. This causes renal vasoconstriction, which combined with low circulation volume leads to starvation of blood to the kidney. This leads to rapid deteriorating kidney function. Hepatorenal syndrome is fatal within a week or so unless liver transplant is performed.

Question 30

What causes hepatic encephalopathy?

Answer 30

thought to be caused by the build up of toxins that affect the brain. One toxin that is particularly worth remembering is ammonia, which is produced by intestinal bacteria

Question 31

How does ammonia build up

Answer 31

the functional impairment of the liver cells prevents them metabolising the ammonia into harmless waste products. Secondly, collateral vessels between the portal and systemic circulation mean that the ammonia bypasses liver altogether and enters the systemic system directly.

Question 32

How does hepatic encephalopathy present?

Answer 32

Acutely, it presents with reduced consciousness and confusion. It can present in a more chronically with changes to personality, memory and mood.

Question 33

Hepatic encephalopathy precipitating factors

Answer 33

Constipation
Electrolyte disturbance
Infection
GI bleed
High protein diet
Medications (particularly sedative medications)

Question 34

Management of hepatic encephalopathy

Answer 34

Laxatives (i.e. lactulose) promote the excretion of ammonia. The aim is 2-3 soft motions daily. They may require enemas initially.
Antibiotics (i.e. rifaximin) reduces the number of intestinal bacteria producing ammonia. Rifaximin is useful as it is poorly absorbed and so stays in the GI tract.
Nutritional support. They may need nasogastric feeding.