Types of Liver Disease

Question 1

How many different types of liver disease are there?

Answer 1

200 types

Question 2

What is the prevalence of liver disease in the UK?

Answer 2

2 million, with the prevalence increasing

Question 3

What are the main causes of LD?

Answer 3

Obesity
Alcohol - the main cause
Undiagnosed hepatitis infection
Drug or other chemical toxicity

Question 4

State the different types of LD?

Answer 4

Alcohol related liver disease
Drug induced hepatoxicity
Hepatitis
Non-alcoholic fatty liver disease
Cirrhosis
Cancer
Gallstones
Cholangitis
Hemochromatosis
Wilson’s disease
Gilbert’s disease

Question 5

What are the main causes of hepatitis?

Answer 5

Mainly viral causes - in particular Hepatitis B and C can cause long-term inflammation

Other causes include:
Heavy alcohol use
Toxins
Drug induced
Autoimmune disease

Question 6

What is non-alcoholic fatty liver disease?

Answer 6

It is a term used for a range of conditions caused by a build of fat within the liver and is usually seen in patients that are overweight or obese. Fat is usually stored in the adipose but the liver does have some capability to also store some fat. In fatty liver large vacuoles of TG accumulate in hepatocytes via steatosis.
Early stage fatty liver disease is not harmful but in later stages can progress to cirrhosis.

Question 7

What percentage of US adults have fatty liver?

Answer 7

It is believed to affect 20-30% of US adults.

Question 8

Describe the potential progression of fatty liver disease?

Answer 8

Increased TG deposition within hepatocytes results in a ‘fatty liver’ indicated by increased TG and LFTs, alongside liver fat.
15-20% then develop non-alcohol fatty liver disease resulting in inflammation and fibrosis of the liver which can then develop into cirrhosis and then potentially a hepatocellular carcinoma.

Question 9

What are gallstones?

Answer 9

Gallstones are deposits of hardened, solidified substances found in bile such as cholesterol which are abnormally formed within the gallbladder or bile duct. This can block bile secretion from the liver known as bile duct obstruction and cause of a backlog causing infection and inflammation possibly resulting in acute cholecystitis (inflammation of the gallbladder wall).

However most cases of gallstones don’t present with symptoms and do not need to be treated (may not cause complete biliary obstruction).

Question 10

What are the risk factors for gallstones?

Answer 10

Being overweight or obese
Female (particular if you have children)
Increasing age

Question 11

What is Cholangitis?

Answer 11

Cholangitis is inflammation of the bile duct, this is different for cholecystitis which is inflammation of the gallbladder wall. However presence of gallstones does increase the risk of cholangitis occurring. Again this can cause narrowing of the bile duct leading to complications.

Question 12

What are the risk factors for Cholangitis?

Answer 12

Aside from gallstones other risk factors include:
Having autoimmune diseases such as inflammatory bowel disease (ulcerative colitis or Crohn’s disease)
Recent medical procedures involving the bile duct area
Having human immunodeficiency virus (HIV)
Traveling to countries where you might be exposed to worms or parasites

Question 13

What is hemochromatosis?

Answer 13

This is an inherited condition which causes your body to absorb too much iron from the food you eat. When untreated this can result in iron deposition in tissue and organs including the liver, heart and pancreas resulting in complications.

Question 14

What is Wilson’s disease?

Answer 14

Another rare inherited condition which causes copper overload due to the inability of the liver to process and eliminate copper. The accumulated copper within hepatocytes causes inflammation, damage and in some cases scarring (fibrosis) in your liver, known as hepatitis which in some cases can develop into cirrhosis.

Question 15

What is Gilbert’s syndrome?

Answer 15

Gilbert’s syndrome (GS) is a condition in which you have higher than normal amounts of bilirubin in your blood, also known as unconjugated hyperbilirubinemia. The syndrome is relatively common (1/20 are affected) and is due to the inability of the liver to metabolise bilirubin.

Question 16

Describe the differences between acute and chronic liver disease.

Answer 16

Acute LD is generally caused by viruses or drug causing damage to hepatocytes and inflammation. However in acute LD (less than 6 months) the ability of hepatocytes to regenerate very efficient and therefore any inflammation resolves within a couple of weeks. However in some cases (such as paracetamol induced hepatoxicity) the extent of damage to hepatocytes is too severe and can be fatal.

Chronic LD is defined by inflammation persistent for over 6 months resulting in permanent damage with structural changes to hepatocytes leading to cirrhosis and can lead to liver cancer. Unlike acute LD the most common cause of Chronic LD is alcohol abuse.

Question 17

Describe the first stage of progression of liver damage.

Answer 17

Liver disease begins with a chronic injury, damaging hepatocytes and leading to the recruitment of pro-inflammatory cytokines resulting in matrix deposition. There is also cell death of hepatocytes and other cells present in the liver lobules, in angiogenesis occurs. This develops into early fibrosis.

Question 18

What are some of the possible causes of chronic injury resulting in the first stage of LD?

Answer 18

Viral infection
Alcohol
Non-alcoholic steatohepatitis
Autoimmune disorders
Cholestatic disorders
Metabolic diseases

Question 19

Following early fibrosis what is the next stage in Liver disease?

Answer 19

In early fibrosis, hepatocytes begin to die/loss of function and are unable to regenerate fully (known as aberrant hepatocytes regeneration). Due to matrix deposition disrupted architecture occurs these structural changes resulting in cirrhosis of the liver potentially causing liver failure and portal hypertension.
Hepatocellular carcinoma can also occur in late stage liver disease, and at this stage the only treatment is a liver transplant.

Question 20

Which stages of Liver Disease is the damage reversible?

Answer 20

Up to early fibrosis of the liver, treating the underlying cause (such as weight loss in fatty liver) or by treatment of anti-fibrotic drugs, resolution can occur with physiology returning to that of a healthy liver.
These same treatment strategies don’t achieve the same results when it is damaged has progressed to cirrhosis, but some regression can occur.

Question 21

What is the timeline from chronic injury to cirrhosis/liver failure?

Answer 21

Anything between 5-50 years depending on the individual. Genetic polymorphisms, epigenetic markers and presence of co-factors such as obesity and alcohol can all influence the rate of liver damage.

Question 22

Describe the structural and cell changes that occur in liver lobules with advanced fibrosis.

Answer 22

Firstly there is a dramatic increase in hepatic stellate cells causing ECM deposition and facilitating fibrosis. There is infiltration of lymphocytes and constant activation of Kupffer cells in the attempt to phagocytose any dead cells including hepatocytes.
There is increased resistance of the sinusoid lumen to blood flow due to fibrotic tissue, resulting in portal hypertension.

Question 23

Describe the route of transmission of the six different types of Hepatitis infection.

Answer 23

Hepatitis A - faecal to oral
Hepatitis B - bodily fluid, blood, mother to baby
Hepatitis C - bodily fluids
Hepatitis D - bodily fluids
Hepatitis E - contaminated food and water, faecal to oral
Hepatitis G - bodily fluids

Question 24

Describe the type of inflammation each Hepatitis infection causes?

Answer 24

Hepatitis A - causes acute inflammation, usually self-limiting
Hepatitis B - cause acute inflammation which can then develop into chronic inflammation into cirrhosis and potentially a hepatocellular carcinoma
Hepatitis C - causes chronic inflammation
Hepatitis D - acute or chronic infection however needs Hep B to survive
Hepatitis E - self-limiting
Hepatitis G - chronic infection/inflammation similar to Hepatitis C virus

Question 25

Which Hepatitis infections are their vaccines available against?

Answer 25

Hepatitis A vaccine (not prevalent in the UK but is in parts of the world where Hep A is more common)
Hepatitis B vaccine (given at 8,12 and 16 weeks as part of the 6 in 1 vaccine).

Question 26

What is drug induced hepatoxicity?

Answer 26

Drug induced hepatoxicity can occur from prescribed drugs, herbal remedies (which have a high association with hepatoxicity).
Drugs can either cause inflammation (hepatitis) or permanent damage in overdose, long-term use, inappropriately prescribed or idiosyncratically.

Question 27

What are some of the drugs that can cause hepatoxicity?

Answer 27

Very extensive list but does include:
Statins
Methotrexate
Long-term antibiotics - amoxicillin and tetracyclines increase LFTs

Question 28

What are some of the natural products that cause liver damage?

Answer 28

Herbal remedies
High doses of Vitamin A
Wild mushrooms (liver failure)

Question 29

What is the most common cause of LD/Cirrhosis?

Answer 29

Alcohol

Question 30

At what alcohol intake does liver damage occur?

Answer 30

> 40 grams/day in men and >20 grams/day in women

Reference: 1 unit = 9 grams

Question 31

What are the healthy living guidelines regarding alcohol intake?

Answer 31

Men and women are advised not to drink more than 14 units a week on a regular basis
Spread your drinking over 3 or more days if you regularly drink as much as 14 units a week
Avoid binge drinking and try to have two alcohol free days each week

Question 32

How does alcohol damage hepatocytes?

Answer 32

Alcohol and its toxic metabolites can directly damage key liver cells (primarily hepatocytes and parenchymal cells) through the excessive generation of molecules called free radicals. This causes inflammation which causes fibrosis and develop into cirrhosis if abstinence is not achieved.
Fibrosis alters structure causes portal hypertension and eventual liver failure.

Question 33

What is cholestasis?

Answer 33

Cholestasis is defined as a decrease in bile flow due to impaired secretion by hepatocytes or to obstruction of bile flow through intra-or extrahepatic bile ducts

Question 34

What are the potential causes of lack of bile synthesis in cholestasis?

Answer 34

Caused by hepatitis from viruses, alcohol, drugs or in pregnancy.

Question 35

What are the causes of bile duct obstruction in cholestasis?

Answer 35

Gall stones, carcinoma (cancerous growth), cholangitis

Question 36

What are some of the symptoms you would expect in a patient with acute LD?

Answer 36

A lot of patient’s are asymptomatic but symptoms can include:
General malaise
Anorexia
Fever
Jaundice

Question 37

What are some of the symptoms in chronic LD?

Answer 37

Fatigue, weakness
Weight loss due to the inability to metabolise and synthesis amino acids
Nausea and vomiting
Cachexia
Abdominal swelling
Right upper quadrant pain and tenderness
Jaundice

Question 38

Which other more specific symptoms may you expect for LD?

Answer 38

Symptoms may be present due to a specific disease state:
For example in Gallstones you may experience abdominal pain and nausea and vomiting after eating

If the gallstones become infected, a persistent fever may occur

Question 39

Loss of which physiological processes occur as a result of liver failure?

Answer 39

Inability to metabolise waste and therefore resulting in a build of toxins and waste products for example bilirubin resulting in deposition in tissue
Failure to to produce proteins required for body function such as clotting factors (leading to bruising) and loss of albumin leading to swelling

Question 40

What are some of the progressive symptoms of LD (Cirrhosis)?

Answer 40

Easy bruising due to lack of clotting factors
Gynecomastia (increased male breast size)
Impotence
Confusion
Ascites
Portal hypertension
Oesophageal varices

Question 41

Describe and explain the features of jaundice.

Answer 41

Jaundice is characterised by discolouration of the skin and mucus membranes (yellowing of the skin and eyes) due to accumulation and deposition of bilirubin.

There are three causes of bilirubin build up:
Haemolysis - excessive breakdown of red blood cells
Hepatocellular damage
Cholestasis -

Question 42

What are the three causes of bilirubin build up?

Answer 42

Haemolysis - excessive breakdown of red blood cells, liver is unable to process heme
Hepatocellular damage
Cholestasis - bile is made by the liver but is unable to be eliminated due to obstruction in the bile duct

Question 43

Explain the pathophysiology of portal hypertension and oesophageal varices.

Answer 43

Liver cirrhosis causes structural changes within the liver and hardening causes resistance to portal blood flow. This leads to a backlog and with increased pressure in the portal vein is known as portal hypertension.
High blood pressure redistributes blood into surrounding blood vessels including thin-walled veins in the oesophagus close to the surface and upper stomach. These veins are not used to withstanding high pressure and are vulnerable to bursting resulting in hypovolemic shock and death.

Question 44

Describe and explain the features of ascites.

Answer 44

Ascites presents as a distinctive swelling of the abdomen as a result of an accumulation of fluid within the peritoneal cavity.
This results as a pressure imbalance between within the circulation (which is high) and outside (the peritoneal cavity which is low). Fluid moves from high to low pressure.

Question 45

What are some of the causes of ascites formation?

Answer 45

Portal hypertension
Low plasma albumin - albumin usually maintains osmolality - helping fluid stay in the blood vessels instead of leaking into the tissues, modulating the distribution of fluid between body compartments
Na+/Water retention - any kidney failure can induce ascites

Question 46

Explain the pathophysiology of hepatic encephalopathy.

Answer 46

Hepatic encephalopathy is a characterised neuropsychiatric abnormalities resulting from the accumulation of neurotoxic substances in the bloodstream. These neurotoxic substances are usually metabolised and eliminated by the liver but in advanced liver disease there is a reduced ability of the liver to do this. An example is nitrogenous waste products. The liver is responsible for metabolising ammonia to urea which is then eliminated by the kidneys. In advanced LD, the inability of the liver to metabolise ammonia results in accumulation and at high concentrates becomes soluble across the BBB causing neurological disturbances.

Question 47

What is associated with hepatic encephalopathy?

Answer 47

Portal systemic bypassing of the liver
Cirrhosis
Acute liver failure

Question 48

What are some of the consequences of hepatic encephalopathy?

Answer 48

Altered mental state
Fetor hepaticus (characteristic breath of patients with severe LD- rotten eggs and garlic)
Asterixis- hand tremor
Drowsiness
Confusion
Coma

Question 49

What is hepatic encephalopathy precipitated by?

Answer 49

Dehydration
Hypovolemia
GI bleed
CNS drugs
Alcohol
High dietary protein
Constipation

Question 50

What is Wernicke’s encephalopathy?

Answer 50

Altered mental state resulting as a consequence of thiamine deficiency. This is experienced in chronic alcohol abuse as alcohol leads to a reduction in absorption of thiamine (Vitamin B1). Wernicke’s encephalopathy has similar presentation to that of hepatic encephalopathy.

Question 51

Explain the pathophysiology of anaemia in LD.

Answer 51

Can occur as a result of:
Portal hypertension causing splenomegaly (enlargement of the spleen) decreasing the number of red blood cells in circulation, resulting megaloblastic anaemia.
Alcohol is directly toxic to the bone marrow
Reduction in clotting factor synthesis

Question 52

What are some of the circulatory and skin changes that occur in LD?

Answer 52

Circulatory:
Palmer erythema (no dryness just redness in the palms)
Spider naevi - visible clusters of red veins on the face also associated with oesophageal varices as a consequence of back pressure
Finger clubbing-changes in interstitial fluid also seen in lung cancers

Skin:
Pruitis- intense itching due to accumulation of waste/toxic substance deposition in the dermis.