Abnormal Liver Function

Question 1

What is the most common cause of liver disease in the UK?

Answer 1

NAFLD (20-30% of the population)

Question 2

What is the most common cause of liver death?

Answer 2

Alcoholic Liver Disease (84% of deaths from liver disease)

Question 3

Describe the 4 stages of alcoholic liver disease

Answer 3

Normal –> Steatosis –> Steatohepatitis –> Fibrosis/Cirrhosis

Question 4

Describe Charcots Triad of Cholangits

Answer 4

Fever (with rigors) + RUQ pain + Jaundice

Question 5

What type of liver disease is pruritis associated with?

Answer 5

Cholestatic diseases

Question 6

What LFTs would indicate a cholestatic picture?

Answer 6

Raised Alk Phos, Bilirubin and Gamma GT

Question 7

What LFTs would indicate hepatocellular injury?

Answer 7

Raised “transaminases”

ALT and AST

Question 8

Does how much the transaminases are raised indicate a certain diagnosis?

Answer 8

Mildly raised (1.5-3x normal) = ALD/NAFLD
Significantly raised (>3) = viral, drug and autoimmune hepatitis

Question 9

What level does the bilirubin have to be to be a clinical jaundice AND to see a visible jaundice?

Answer 9

> 30 micromol/L = Clinical Jaundice

> 50 micromol/L = Visible Jaundice

Question 10

What are the causes of unconjugated jaundice?

Answer 10

Gilberts or Haemolysis

all others have a mixed or conjugated picture

Question 11

Describe what happens to coagulation studies and why in liver disease.

Answer 11

Increased prothrombin (PT) time due to reduced synthesis of vitamin K dependent clotting factors by the liver. 
Should be excluded from Vit K deficiency which can commonly occur in biliary obstruction as reduced bile salts in the intestine cause reduced absorption of Vitamin K.

Question 12

What is the tumour marker tested for in hepatocellular carcinoma?

Answer 12

alpha - fetoprotein

Question 13

What is the tumour marker tested for in cholangiocarcinoma?

Answer 13

Ca 19.9

Question 14

List some of the common indications for liver biopsy

Answer 14

Diagnosis and Staging of Fibrosis
Focal Liver Lesions (guided)
Post Transplant - rejection

Question 15

List some of the other non-invasive methods of staging fibrosis?

Answer 15

NAFLD Fibrosis Score
Transient Elastography (Fibroscan)
Blood Tests ?ALT role

Question 16

In Liver disease, what does a large spleen indicate?

Answer 16

Portal Hypertension

Question 17

Describe the diagnostic criteria for Metabolic Syndrome

Answer 17

Any 3 of the following: 
Increased weight circumference (or BMI >30)
Raised Triglycerides
Reduced HDL-cholesterol
Raised Blood Pressure
Raised Fasting Plasma Glucose

Question 18

What does a serum lipid profile test include?

Answer 18

Total Cholesterol
HDL
LDL
Triglycerides

Question 19

What sign on Liver US would indicate NAFLD

Answer 19

Bright Liver

Question 20

Why are beta blockers used in patients at risk of variceal haemorrhage or as secondary prevention following a variceal haemorrhage?

Answer 20

They reduce portal pressures by decreasing cardiac output
They also cause splanchnic vasocontriction (increase in splachnic blood blow in portal hypertension contributes to the hyper-dynamic state and worsens the effects of cirrhosis and portal hypertension)

Question 21

In patients with cirrhosis, describe the surveillance for hepatocellular carcinoma

Answer 21

6 monthly alpha feta protein measurements and liver ultrasound

Question 22

Describe hepatopulmonary syndrome

Answer 22

Triad of Liver Disease, hypoxaemia and evidence of pulmonary vessel dilatation.

Question 23

Describe hepatorenal syndrome

Answer 23

A complication of end-stage liver disease which occurs in patients who have chronic liver dysfunction with cirrhosis and ascites and also in acute liver failure. In hepatorenal syndrome (HRS) there is impaired renal function which is often precipitated by events lowering blood pressure.

Question 24

Briefly summarise the management for NAFLD

Answer 24

Diet (calorie restrict)
Increase Exercise
Orlistat
Bariatric Surgery
Pioglitazone
Vitamin E

Question 25

Describe the role of Hepatic Stellate cells in development of cirrhosis

Answer 25

In quiescent state - act as a store for Vitamin A in the liver They are activated in response to injury and lay down collagen - the fibrous tissue which forms the bands which make up cirrhosis.

Question 26

What are the 4 important sings of decompensation in chronic liver disease?

Answer 26

Jaundice Encephalopathy Ascites Asterixis

Question 27

Describe the role of Child-Pugh score in Liver Disease

Answer 27

Used to assess liver function and prognosis in cirrhotic patients. It measures Bilirubin, ascites, albumin, INR/PTT and encephalopathy

Question 28

Describe the Model of End Stage Liver Disease (MELD) score in Liver Disease

Answer 28

Used to prioritize patients for liver transplant. It measures Bilirubin, creatinine and INR

Question 29

Described the three pathophysiology drivers of ascites

Answer 29

Essentially, on a background of chronic liver disease there is likely to be vasodilatation. Vasodilatation = reduced perfusion of the kidneys. Kidneys programmed though renin-angiotensin system that when they are hypoperfused they should retain salt and water Portal hypertension - exerts local hydrostatic pressure and leads to transudation of fluid into the peritoneal cavity Low serum albumin may further contribute by a reduction in plasma oncotic pressure

Question 30

Describe the Serum Ascites Albumin Gradient, and what different values mean

Answer 30

``` High Gradient (>1.1 g/L) suggests portal hypertension as the cause Low Gradient ( 97% accuracy) ```

Question 31

What condition should be suspected in any person with ascites who deteriorates suddenly?

Answer 31

Spontaneous Bacterial Peritonitis

Question 32

What investigation would you do to confirm spontaneous bacterial peritonitis?

Answer 32

Check for neutrophils in the ascitic fluid, if present = evidence enough to start treatment

Question 33

Recurrence of SBP is high, up to 70% in the first year, what can be done for prophylaxis?

Answer 33

An oral quinolone antibitoic

Question 34

Describe the difference between Type 1 and Type 2 Hepatorenal Syndrome

Answer 34

Type 1 - rapidly progressive, usually occurs with acute liver failure, clinical pattern of acute renal failure - DIE OF Type 2 - Moderate renal failure with steady, slow progressive course, clinical pattern of refractory ascites - DIE WITH

Question 35

Describe the pathophysiology of hepatic encepaholpathy.

Answer 35

In cirrhosis the portal blood bypasses the liver via the collaterals and the "toxic" metabolites pass directly into the brain to produce the encephalopathy. An acute onset usually has a precipitating factor e.g. high dietary protein, GI haemorrhage, SBP

Question 36

Describe the 4 grades of hepatic encephalopathy

Answer 36

``` Grade 1 Lack of awareness Grade 2 Lethargy or apathy Grade 3 Somnolence or semi-stupor Grade 4 Coma - unresponsive to verbal or noxious stimuli ```

Question 37

How are cirrhotic patients monitored for oesophageal varicies at risk of bleeding?

Answer 37

OGD at diagnosis of cirrhosis and every 2 years after | Beta blocker as primary prevention for variceal haemorrhage

Question 38

Over 90% of liver tumours are secondary. What common primary tumours metastasise to liver?

Answer 38

Bowel Lung Breast

Question 39

Describe the main risk factors for developing HCC

Answer 39

Hep B or Hep C infection (important globally, esp where Hep B is endemic) Alcoholic Cirrhosis NAFLD

Question 40

Where do HCCs commonly metastasise to?

Answer 40

Regional lymph nodes, bones and lungs

Question 41

Describe how CT is used to diagnose HCC

Answer 41

4-Phase CT - in arterial phase tumour is white as highly vascularised, in venous phase, tumour looks blacker than rest of liver Can diagnose HCC in patients with these CT findings with 99% accuracy

Question 42

Describe the pathophysiology behind low platelets in liver disease

Answer 42

Splenomegaly caused by portal hypertension, leads to pooling and sequestration of platelets in he spleen Also decreased production of thrombopoeitin by the liver leads to decreased thrombopoeisis in the bone marrow.

Question 43

The terms Fulfilmant Hepatic Failure and Acute Hepatic failure are often used interchangeably. HOWEVER, what does the word fulfilmant specifically imply?

Answer 43

The presence of encephalopathy AND the absence of pres-existing liver disease (makes it clinically significant from acute on chronic liver disease)

Question 44

What is the commonest cause of fulfilmant hepatic failure in the UK and what is commonest cause worldwide?

Answer 44

``` UK = paracetamol poisoning (>50%) Globally = viral hepatitis ```

Question 45

How common is cerebral oedema in fulfilmant hepatic failure?

Answer 45

Up to 80% of patients get it | 25% of all deaths from FHF attributable to it

Question 46

Describe the pathophysiology of cerebral oedema in FHF

Answer 46

Patients with liver dysfunction have impaired urea synthesis The brain acts as an alternative ammonia detoxification pathway. Ammonia combines with glutamate in astrocytes to from glutamine. Glutamine attracts water into astrocytes causing them to swell. Astrocyte swelling and increased brain water = cerebral oedema Cerebrel oedema causes intracranial hypertension, raised ICP and brain herniation

Question 47

Describe the other effects FHF has due to loss of metabolic function in the liver.

Answer 47

Decreased gluconeogenesis = hypoglycemia Decreased lactate clearance = lactic acidosis Decreased synthetic capacity = coagulopathy

Question 48

What investigations would you do in a patient who presented with symptoms of FHF?

Answer 48

Paracetamol levels Hepatitis Screen Auto-antibody screen Screen for Wilsons - 24 hr urine copper and Caeruloplasmin levels

Question 49

Whether FHF is defined as Hyper-acute, Acute or Sub-acute is dependent on the time from jaundice to hepatic encephalopathy, what are those time parameters?

Answer 49

``` Hyper-acute = 0-7 days Acute = 8-28 days Sub-Acute = 1-3 months ```

Question 50

What signs would you find on examination in a patient presenting with FHF?

Answer 50

Jaundice, small liver, signs of encephalopathy, fetor hepaticus fever, vomitng, hypotension and hypoglycemia occur Neurological examination shows spasticity and hyperreflexia

Question 51

Why should metformin be suspended n | in patients who are having a CT scan?

Answer 51

If the contract medium causes renal failure Metformin is excreted primarily be the kidneys Continued intake of metformin results in a toxic accumulation of the drug and subsequent lactic acidosis. To avooid this complication metformin should be suspended after the administration of the contrast agent for 48 hours, during which the contrast induced renal failure will become apparent. If renal function is normal at 48 hours then metformin can be restarted.

Question 52

Describe the typical population affected by PBC

Answer 52

90% of those affected are WOMEN in the age range of 40-50

Question 53

Describe the clinical features of PBC

Answer 53

Pruritis - typically worse on palms and soles at night time Fatigue - can be disabling Dry eyes and mouth (sicca symptoms) - seen in 70% cases Poor memory Liver Sx e.g. jaundice, hepatomegaly,

Question 54

Describe the three things used to diagnose PBC

Answer 54

Abnormal LFTs (cholestatic raised ALP) Positive AMA Compatible Histology (rarely done now as AMA so useful) ESSENTIALLY AMA AND RAISED ALP THINK PBC

Question 55

Describe the pathophysiology of PBC

Answer 55

Progressive destruction of small bile ducts through immune infiltration leads to biliary cirrhosis *Granulomatous*

Question 56

Describe the treatment for PBC

Answer 56

DISEASE PROGRESSION UCDA (ursodeoxycholic acid) is the only licenced therapy for PBC. 80% have a full response rate. Transplantation if not effective or refractory SYMPTOM RELIEF Itch - cholestyramine Fatigue - no Tx

Question 57

Describe the two types of autoimmune hepatitis

Answer 57

Type 1 = 74% cases, all ages, ANA/ASMA. Patients may be aymptomatic, have abnormal LFTS or signs of chronic liver disease on examination Type 2 -

Question 58

What two test results in combination would make you consider autoimmune hepatitis?

Answer 58

ANA/ASMA and raised IgG

Question 59

Describe the pathophysiology of PSC

Answer 59

PSC occurs because of inflammation in the bile ducts , which results in hardening (sclerosis) and narrowing of the bile ducts both inside and outside of the liver. The resulting scarring of the bile ducts blocks the flow of bile, causing cholestasis

Question 60

Describe the typical population affected by PSC

Answer 60

70% are male and average age of onset is 40 years

Question 61

What condition is commonly associated with PSC?

Answer 61

IBD (60-80% of patients with PSC have IBD - everyone diagnosed with PSC should undergo colonoscopy If they are found to have IBD - should be regularly screened for colorectal cancer)

Question 62

Describe the presentation of patients with PSC

Answer 62

With increasing screening of patients with IBD, PSC is often detected in the aymptomatic phase wiith abnormal liver biochemistry (usually increased ALP) Symptomatic presentation is usually with fluctuating pruritis, fatigue, jaundice, RUQ pain and cholangitis

Question 63

What antibody is associated with PSC?

Answer 63

ANCA is found in 60% of cases

Question 64

Describe what you would see on imaging of a patient with PSC

Answer 64

Ultrasound - will appear normal MRCP - see multifocal strictures and segmental dilatation of bile ducts MRCP may fail to idenify minor (but clinically significant) intrahepatic changes, these will have to be picked up on ERCP

Question 65

How is the scar tissue of PSC classically described on histology?

Answer 65

onion skin

Question 66

What cancer are people with PSC at significantly increased risk of?

Answer 66

Cholangiocarcinoma - patients should be screened by checking Ca 19.9 tumour marker)

Question 67

Can PSC be cured with tranplantation?

Answer 67

No - it can return after transplantation and each transplantation increases mortality signifcantly

Question 68

What two investigation results in combination would make you think of PSC

Answer 68

Raised ALP and ANCA