Liver Disease

Question 1

Alcoholic Liver Disease stages / stepwise progression

Answer 1

1. Alcohol related fatty liver

Drinking leads to a build-up of fat in the liver. If drinking stops this process reverses in around 2 weeks.

2. Alcoholic hepatitis

Drinking alcohol over a long period causes inflammation in the liver sites. Binge drinking is associated with the same effect. Mild alcoholic hepatitis is usually reversible with permanent abstinence.

3. Cirrhosis

This is where the liver is made up of scar tissue rather than healthy liver tissue. This is irreversible. Stopping drinking can prevent further damage. Continued drinking has a very poor prognosis.

Question 2

recommended alcohol consumption

Answer 2

do not regularly drink more than 14 units per week for women and men

spread over 3 days or more, no more than 45 units per day

Question 3

CAGE questions

Answer 3

The CAGE question can be used to quickly screen for harmful alcohol use:

C – CUT DOWN? Ever thought you should?
A – ANNOYED? Do you get annoyed at others commenting on your drinking?
G – GUILTY? Ever feel guilty about drinking?
E – EYE OPENER? Ever drink in the morning to help your hangover/nerves?

Question 4

complications of alcohol

Answer 4

Alcoholic Liver Disease
Cirrhosis and the complications of cirrhosis including hepatocellular carcinoma
Alcohol Dependence and Withdrawal
Wernicke-Korsakoff Syndrome (WKS)
Pancreatitis
Alcoholic Cardiomyopathy

Question 5

signs of liver disease

Answer 5

Jaundice
Hepatomegaly
Spider Naevi
Palmar Erythema
Gynaecomastia
Bruising – due to abnormal clotting
Ascites
Caput Medusae – engorged superficial epigastric veins
Asterixis – “flapping tremor” in decompensated liver disease

Question 6

investigations for alcoholic liver disease

Answer 6

bloods

FBC – raised MCV
LFTs – elevated ALT and AST (transaminases) and particularly raised gamma-GT. ALP will be elevated later in the disease. Low albumin due to reduced “synthetic function” of the liver. Elevated bilirubin in cirrhosis.
Clotting – elevated prothrombin time due to reduced “synthetic function” of the liver
U+Es may be deranged in hepatorenal syndrome.

Ultrasound

An ultrasound of the liver may show fatty changes early on described as “increased echogenicity”. It can also demonstrate changes related to cirrhosis if present.

“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.

Endoscopy

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

CT and MRI scans

CT and MRI can be used to look for fatty infiltration of the liver, hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes and ascites.

Liver Biopsy

Liver biopsy can be used to confirm the diagnosis of alcohol related hepatitis or cirrhosis. NICE recommend considering a liver biopsy in patients where steroid treatment is being considered.

Question 7

general management of ALD

Answer 7

Stop drinking alcohol permanently
Consider a detoxication regime
Nutritional support with vitamins (particularly thiamine) and a high protein diet
Steroids improve short term outcomes (over 1 month) in severe alcoholic hepatitis but infection and GI bleeding need to be treated first and do not improve outcomes over the long term
Treat complications of cirrhosis (portal hypertension, varices, ascites and hepatic encephalopathy)
Referral for liver transplant in severe disease however they must abstain from alcohol for 3 months prior to referral

Question 8

alcohol withdrawal symptom

Answer 8

6-12 hours: tremor, sweating, headache, craving and anxiety
12-24 hours: hallucinations
24-48 hours: seizures
24-72 hours: “delerium tremens”

Question 9

delirium tremens

Answer 9

medical emergency of alcohol withdrawal

alcohol stimulates GABA receptors (relax) and inhibits glutamate receptors /NMDA (inhibitory effect on the electrical affect of brain)

chronic alcohol- GABA up regulated, glutamate down regulated

remove alcohol- GABA under functions, glutamate over functions

extreme excitability of the brain = excess adrenergic activity.

Acute confusion
Severe agitation
Delusions and hallucinations
Tremor
Tachycardia
Hypertension
Hyperthermia
Ataxia (difficulties with coordinated movements)
Arrhythmias

Question 10

managing alcohol withdrawl

Answer 10

CIWA-Ar= tool*

Benzodiazepines= chlordiazepoxide (librium)
(diazepam less common alternative)
10-40mg every 1-4 hours continued for 5-7 days

IV high dose B vitamins (pabrinex) followed by a regular lower dose of thiamine

Question 11

WKS- Wernicke Korsakoff Syndrome

Answer 11

Alcohol excess leads to thiamine (vitamin B1) deficiency. Thiamine is poorly absorbed in the presence of alcohol and alcoholics tend to have poor diets and rely on the alcohol for their calories. Wernicke’s encephalopathy comes before Korsakoffs syndrome. These result from thiamine deficiency.

werkicker’s:

• confusion
• oculomotor disturbances
• ataxia

korsakoff:

• memory impairment (retrograde, anterograde)
• behavioural changes

Question 12

wernicker’s encephalopathy

Answer 12

medical emergency
high mortality rate
often irriversible
full time institutional care

prevention- thiamine and abstain from alcohol

Question 13

what is liver cirrhosis

Answer 13

chronic inflammation and damage to liver cells. replaced with scar tissues (fibrosis) and nodules of scar tissues in the liver.

this effects the blood flow through the liver which causes increased resistance in the vessels (portal hypertension)

Question 14

most common causes of liver cirrhosis

Answer 14

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

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

Question 15

signs of cirrhosis

Answer 15

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 16

liver cirrhosis investigations

Answer 16

bloods:

• LFT deranged in decompensated
• albumin and prothrombin (synthetic function of the liver)
• hyponatraemia if fluid retention
• urea and creatinine (hepatorenal syndrome)
• viral markers
• alpha feta protein (tumor marker for hepatocellular carcinoma) (check every 6 months)
• ultrasound

Question 17

Enhanced Liver Fibrosis (ELF) blood test

Answer 17

first line recommended investigation for assessing fibrosis in non-alcoholic fatty liver disease but it is not currently available in many areas and cannot be used for diagnosing cirrhosis of other causes. It measures three markers (HA, PIIINP and TIMP-1) and uses an algorithm to provide a result that indicates the fibrosis of the liver:

< 7.7 indicates none to mild fibrosis
≥ 7.7 to 9.8 indicates moderate fibrosis
≥ 9.8 indicates severe fibrosis

Question 18

ultrasound cirrhosis

Answer 18

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 19

Fibroscan

Answer 19

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 20

liver cirrhosis imaging

Answer 20

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

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

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

• Child Pugh’s score
• MELD score

Question 21

general management of lier cirrhosis

Answer 21

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 22

complications of liver cirrhosis

Answer 22

Malnutrition and muscle wasting (increased use of muscle tissue as fuel an reduces the protein avaiabiliy in the body for muscle growht) (disruption of the ability to store glucose as glycogen and release when its required))

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

• regular meals
• low sodium
• high protein, high calorie
• avoid alcohol

Question 23

what delivers blood to the liver?

Answer 23

portal vein (from the superior mesenteric vein) 
splenic vein

Question 24

portal hypertension and varices

Answer 24

liver cirrhosis= high resistance of blood flow in the river so there is a backpressure into the portal system

back pressure causes the vessel a the sites where portal system anastomoses with systemic venous system
swollen, tortuous vessels

Gastro oesophageal junction
Ileocaecal junction
Rectum
Anterior abdominal wall via the umbilical vein (caput medusae)

high blood flow= exsanguinate quickly

Question 25

treatment of stable varices:

Answer 25

Propranolol reduces portal hypertension by acting as a non-selective beta blocker
Elastic band ligation of varices
Injection of sclerosant (less effective than band ligation
TIPS

Question 26

TIPS

Answer 26

a technique where an interventional radiologist inserts a wire under xray guidance into the jugular vein, down the vena cava and into the liver via the hepatic vein. They then make a connection through the liver tissue between the hepatic vein and the portal vein and put a stent in place. This allows blood to flow directly from the portal vein to the hepatic vein and relieves the pressure in the portal system and varices. This is used if medical and endoscopic treatment of varices fail or if there are bleeding varices that cannot be controlled in other ways.

Question 27

management of bleeding oesophageal varices

Answer 27

Resuscitation

Vasopressin analogues (i.e. terlipressin) cause vasoconstriction and slow bleeding in varices
Correct any coagulopathy with vitamin K and fresh frozen plasma (which is full of clotting factors)
Giving prophylactic broad spectrum antibiotics has been shown to reduce mortality
Consider intubation and intensive care as they can bleed very quickly and become life threateningly unwell
Urgent endoscopy

Injection of sclerosant into the varices can be used to cause “inflammatory obliteration” of the vessel
Elastic band ligation of varices
Sengstaken-Blakemore Tube is an inflatable tube inserted into the oesophagus to tamponade the bleeding varices. This is used when endoscopy fails.

Question 28

Ascites- clinical features

Answer 28

fluid in peritoneal cavity
increased pressure in portal system causes fluid to leak out of capillaries in the liver and bowel into peritoneal cavity

drop in circulating volme
reduction in BP
RAAS
reabsoorption of fluid and sodium in kidneys

transudative (low protein) content ascites

Question 29

ascites mx

Answer 29

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 30

SBP spontaenous bacterial peritonitis

Answer 30

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).

- asymptomatic
fever
- abdo pain
- deranged bloods (WBC, CRP, creatinine, metabolic acidosis)
- ileus
- hypotension

common organisms:
E.coli, Klebsiella pneumoniae,

Question 31

SBP management

Answer 31

Take an ascitic culture prior to giving antibiotics

Usually treated with an IV cephalosporin such as cefotaxime

Question 32

Hepatorenal syndrome

Answer 32

occurs in liver cirrhosis

hypertension in portal system leads to dilation of the portal blood vessel

leads to a loss of blood vessels in circulation including kidneys. leads to hypotension = RAAS= renal vasoconstriction

the low circulation volume starves the vblood to the kidney

Question 33

hepatic encephalopathy

Answer 33

portosystemic encephalopathy

build up of toxins (ammonia)

ammonia is produced by break down of proteins by intestinal bacteria

builds up when:

1. functional liver cells are impaired so unable to metabolise ammonia into hrmelss waste products
2. collateral vesels between portal and systemic circulation means ammonia is bypassed the liver and therefore enters the systemic directly!

Question 34

hepatic encephalopathy presentation and precipitating factors

Answer 34

acute- reduced consciousness and confusion

chronic- changes to personality, memory and mood

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

Question 35

hepatic encephalopathy management

Answer 35

mx:
1. laxatives (lactulose) to promote the excretion of ammonia from gut. aim for 2-3 soft motions daily. may require enema initially.

2. antbiotic (rifaximin) to reduce the amount of bacteria in the gut producing ammonia. poorly absorbed so stays in GI tract
3. nutritional support - NG feeding

Question 36

NAFLD

Answer 36

metabolic syndrome
increased risk of CVD, stroke, diabetes

fat deposits in liver cells
fat can interfere with functioning liver cells
can progress to hepatitis and cirrhosis

Question 37

NAFLD stages

Answer 37

Non-alcoholic Fatty Liver Disease
Non-Alcoholic Steatohepatitis (NASH)
Fibrosis
Cirrhosis

Question 38

NAFLD risk factors

Answer 38

Obesity
Poor diet and low activity levels
Type 2 diabetes
High cholesterol
Middle age onwards
Smoking
High blood pressure

Question 39

investigate abnormal LFT’s

Answer 39

non invasive liver screen

1. us liver
2. hep b and c serology
3. autoantibodies
4. immunoglobulins (autoimmune hepatitis)
5. wilsons disease (caeruloplasmin)
6. alpha 1 antitrypsin
7. ferritin and transferrin saturation (hereditary haemachromatosis)

Question 40

NAFLD autoantibodies

Answer 40

Antinuclear antibodies (ANA)
Smooth muscle antibodies (SMA)
Antimitochondrial antibodies (AMA)
Antibodies to liver kidney microsome type-1 (LKM-1)

Question 41

investigations for NAFLD

Answer 41

first line:

1. liver US to confirm hepatic steatosis (fatty liver) but does not indicate severity

2. enhanced liver fibrosis (ELF)
measures 3 markers
HA PIINP and TIMP-1
< 7.7 indicates none to mild fibrosis
≥ 7.7 to 9.8 indicates moderate fibrosis
≥ 9.8 indicates severe fibrosis

second line:
NAFLD fibrosis score (if ELF is unavailable) based on an algorithm of age, BMI, liver enzymes, platelets, albumin and diabetes and is helpful in ruling out fibrosis but not assessing the severity when present.

third line:
fibroscan
US that measures the stiffness of the liver and gives indication fo fibroiss.

Question 42

NAFLD management

Answer 42

Weight loss
Exercise
Stop smoking
Control of diabetes, blood pressure and cholesterol
Avoid alcohol
Refer patients with liver fibrosis to a liver specialist where they may treat with vitamin E or pioglitazone.