Abnormal Liver Function (week 5) Flashcards
1
Q
What is the most common cause of liver disease?
A
NAFLD (20-30% of population)
2
Q
What is the most common cause of liver death?
A
Alcoholic liver disease (84%)
3
Q
How does cirrhosis develop from normal liver tissue?
A
Normal –> initial insult to liver (fat or alcohol) = inflammation Steatosis Steatohepatitis Fibrosis –> Cirrhosis (last stage isn’t reversible)
4
Q
What are the complications of liver cirrhosis?
A
Ascites Liver failure Liver cancer Portal HTN (& associated complications) etc.
5
Q
How can cirrhosis present?
A
Incidental findings - Abnormal LFTs, hepatosplenomegaly, raised MCV/abnormal clotting/low platelets Non-specific symptoms - Anorexia, weight loss, lethargy Specific symptoms (usually late stage) - Jaundice, pruritus (itchy skin due to cholestasis), bleeding varices, ascites/oedema, hepatic encephalopathy
6
Q
What does raised alkaline phosphatase and raised gamma GGT indicate?
A
Indicates Cholestasis, malignancy or alcohol abuse
Alcohol will have raised MCV
7
Q
What does increased ALT/AST (the transaminases) indicate?
A
Indicate hepatocellular damage
1.5-3x the upper limit of normal in ALD/NAFLD
> 3x uppler limit of normal in viral, drug induced (paracetamol) and AI hepatitis
8
Q
At what level of bilirubin do you get clinical jaundice?
A
> 30 µmol/L
9
Q
When do you get unconjugated bilirubin?
A
Gilberts, haemolysis, newborn babies (physiological)
10
Q
Which clotting factor(s) are tested in Prothrombin Time (PTT) & therfore, which clotting pathway is being measured?
A
Factor VII.
Extrinsic pathway
11
Q
Why is PTT relevant in liver screening?
A
Liver makes clotting factors II, VII, IX & X. This is disrupted in acute liver failure/damage, which causes the PTT to increase (this happens very quickly).
12
Q
Which autoantibodies do we test for in liver studies? What do they indicate?
A
ANA (antinuclear Ab) & anti SMA (anti smooth muscle Ab) in AI hepatitis.
AMA (anti mitochondrial Ab) in PBC (95%).
(P Billy Connolly is a lAMA)
pANCA in PSC (50%)
(Private Steve Clark is a P wANCA)
13
Q
Which immunoglobulins are measured in liver studies? What do they indicate?
A
Increased IgG - AI hepatitis
Increased IgM - PBC
Increased IgA - Alcoholic liver disease/NAFLD
14
Q
Which tumour markers are relevant to the hepatobiliary system?
A
Alpha fetoprotein - HCC
CA19-9 - Cholangiocarcinoma
15
Q
What is the first line imaging in Hepatobiliary disease? Which others may be helpful?
A
USS - 1st line
CT, MRI, ERCP
16
Q
What are the benefits and limitations of USS in hepatobiliary disease?
A
Good to show obstruction of bile ducts, liver tumour or mass lesion, gallstones and can assess blood flow using doppler function.
Cant assess pancreas well.
17
Q
What are the benefits and limitations of CT in hepatobiliary disease?
A
More sensitive than USS. Excellent investigation for focal liver lesions, varices and evidence of portal hypertension (hypervascularisation)
Needs IV contrast - caution in renal impairment
18
Q
What is the main use of ERCP?
A
To remove stones or to place stents
19
Q
What are the indications for liver biopsy?
A
Chronic liver disease - Diagnosis or staging Focal lesions (guided) Post transplant (rejection)
20
Q
What is the “gold standard” for liver disease staging?
A
Liver biopsy
21
Q
Name 2 scoring systems that can non-invasively assess liver disease
A
FIB-4 score (Age, ALT, AST and platelet count)
NAFLD fibrosis score
22
Q
What is the classical findings in primary biliary cirrhosis (PBC)?
A
AMA +ve
Raised ALP
23
Q
What is PBC are what are the symptoms?
A
Granulomatous inflammation around the small intrahepatic bile ducts
Asymptomatic (incidental finding)
Fatigue, itch, dry eyes and mouth
If severe - symptoms of advanced liver disease
24
Q
What is the diagnostic criteria of PBC?
A
Abnormal LFTs (cholestatic) = Raised ALP
Positive AMA
Compatible Hx
(2 of above = PBC probable, all 3 = definite PBC)
25
What is the treatment for PBC and what is the therapeutic aim?
Ursodeoxycholic acid (UDCA) (S/E = weight gain, hair thinning and diarrhoea)
Fibrates
Transplantation
Treat itch - Cholestyramine, Rifampicin or Naltrexone
26
What is the classical finding in AI hepatitis?
Raised ALT
ANA/ASMA +ve
Raised IgG
27
What are the main types of AI hepatitis? Which autoantibodies do you find for each?
Type 1 (75% of cases & can affect all ages)
ANA/AMSA
Type 2 (<10% of cases & affects young adults)
LKM-1 or LC
28
Is AI hepatitis more common in males or females?
Type 1 - F:M = 3:1
| Type 2 - F:M = 10:1
29
How can AI hepatitis present?
Asymptomatic (incidental finding)
Fatigue, anorexia, nausea, joint pains
Acute hepatitis
Complications of cirrhosis
30
What is the treatment for AI hepatitis? What is the treatment aim/goal?
Immunosuppression - steroids (1st line short term), Azathioprine (1st line long term), Tacrolimus (2nd line)
Transplantation
Aim for normalisation of ALT and IgG
31
What is the classical findings in primary sclerosing cholangitis (PSC)?
Raised ALP
ANCA +ve
(Private Steve Clark is a wANCA)
32
What is PSC and what associated diseases does it have?
Inflammation and fibrosis of intra and extra hepatic bile ducts, causing multifocal strictures
60-80% patients have IBD
(Private Steve Clark is a wANCA and a Incredibly Boring Dude)
33
How does PSC present?
Asymptomatic (incidental finding)
Fatigue, itch, RUQ pain, weight loss
Cholangitis (often not at presentation)
Jaundice and complications of cirrhosis
34
What is the LFT pattern in PSC?
Shows Cholestasis
- -> Increased bilirubin
- -> Increased ALP (indicated obstruction)
35
Apart from blood tests, what investigations are useful in PSC? What would they show?
USS - often normal
MRCP - Multi-focal, short annular strictures alternating with normal or dilated segments (beading)
Liver biopsy - early (often non specific), later = 'Onion skin' fibrosis
36
How do you manage PSC?
Look and test for IBD
If strictures causing symptoms (cholangitis, jaundice, pruritus) - ERCP (insert balloons/stents)
Itch - Cholestyramine, Rifampicin or Naltrexone
Screen for malignancy - Cholangiocarcinoma
37
Summarise PBC - Type of patient, Hallmark LFT/autoantibodies, Symptoms and treatment.
Typical patient - Middle aged women
LFT/Autoantibodies - Raised ALP + AMA +ve
Symptoms - Fatigue, itch, dry eyes & mouth
Treatment - Ursodeoxycholic Acid (UDCA)
P Billy Connolly is a lAMA
38
Summarise AI hepatitis - Type of patient, Hallmark LFT/autoantibodies, Symptoms and treatment.
Typical patient - Any age or sex
LFT/Autoantibodies - Raised ALT + ANA + ASMA
Symptoms - often asymptomatic
Treatment - Immunosuppression
39
Summarise PSC - Type of patient, Hallmark LFT/autoantibodies, Symptoms and Management.
Typical patient - Men
LFT/Autoantibodies - Raised ALP + ANCA +ve
Symptoms - Fatigue, itch, RUQ pain, weight loss
Associated with IBD
Management - Screen for cholangiocarcinoma and bowel cancer
Private Steve Clark is a wANCA and an Incredibly Boring Dude
40
What is AMA associated with?
PBC
41
What is ANA + ASMA associated with?
AI hepatitis
42
What is ANCA associated with?
PSC
43
What is IgA associated with?
Alcohol, NAFLD
44
What is IgM associated with?
PBC
45
What is IgG associated with?
AI hepatitis
46
What are the 2 blood supplies of the liver?
Hepatic artery - Arterial blood from aorta
| Portal Vein - Venous blood from the bowel (2/3)
47
How can we aid prevention of HCC (hepatocellular Carcinoma)?
Primary prevention - HBV vaccine & avoid carcinogens
| Secondary prevention - Reduce alcohol and calorie intake, Reduce exposure to Hep C (increase education)
48
Who do we screen for HCC, how do we do it and how often?
Screen cirrhotic patients
AFP (upper normal limit is 10)
USS - every 6 months - look for liver nodules
If nodule <1cm - scan again in 3 months
If nodule 1-2cm - FNAB looking for HCC
If nodule >2cm - AFP > 400 = HCC (do CT/MRI angiography to stage and confirm HCC)
49
What are the 4 stages of CT or MRI scan for HCC?
Normal scan
Add contrast - Arterial blood supply (aorta/blood seen in white - white areas in liver = HCC) most important stage
Venous stage
Late venous stage
50
Which scoring system do we use to assess liver function? what are the 5 parameters?
Child-Pugh score (5 best function - 15 worst)- looks at fitness to undergo a surgical procedure
Encephalopathy, Ascites, Bilirubin, Albumin, PTT
51
What are the signs of chronic liver disease?
Dupuytrens contracture, palmar erythema, spider naevi (SVC distribution)
Bad signs - Jaundice, ascites, caput medusa, asterixis (liver flap - low level encephalopathy allowing toxins into the blood)
52
What is the most common management of HCC?
TACE (TransArterial ChemoEmbolism)
(blocks off arterial blood supply to tumour - stops growth)
Often precedes the ultimate management is transplant
Also be aware of:
- Single nodule - RESECT
- Advanced with portal invasion - SORAFENIB
53
How does simple steatosis present on biopsy?
Large white adipose cells
54
How do you calculate HVPG (hepatic venous pressure gradient) and what value defines clinically significant portal HTN?
Gradient between Wedged hepatic venous pressure (WHVP) and the free hepatic venous pressure.
It gives an estimate of pressure between the portal vein and IVC.
HVPG >10 defines clinically significant portal HTN
55
What is the formal diagnostic criteria for Acute (fulminant) liver failure (ALF)?
An Increase in PT by 4-6 seconds (INR>1.5)
+ Development of hepatic encephalopathy (HE) = Jaundice
In a patient without preexisting cirrhosis + illness < 6 months
56
What is the most common cause of ALF?
What are some other causes?
Paracetamol OD (toxic = >150mg/kg)
```
Drug reaction
Viral hepatitis
Ischaemic hepatitis
AI hepatitis
Wilsons
Budd Chiari
```
57
What is the mechanism of paracetamol poisoning?
Major route of Paracetamol metabolism:
P metabolised into sulphate and glucuronide (non-toxic) conjugates. This route is easily saturable.
When saturated, minor route of metabolism is used:
P metabolised into NAPQI causing cell death
58
What is the antidote for paracetamol OD? Who do we treat?
Antidote = NAC (N-acetylcysteine)
Treat anyone with paracetamol levels over the "100 line" (100mg/L) - 4 hours after ingestion. (if under, no need treating) Best results within 8 hours.
59
Apart from the antidote, is there any other treatment we can offer?
Activated charcoal (give asap)
60
What is the most apparent LFT in paracetamol OD?
Massive ALT
61
What are the differential diagnoses for massively raised ALT?
Vascular - hypotension, congestion
Viral - Hep A-E, CMV, EBV, HSV, PMV
Drugs/toxins - PARACETAMOL, halothane, Abx, antivirals etc.
62
What are the best prognostic markers in ALF?
Bilirubin and PTT
ALT is a bad prognostic marker. If massively raised (1000's) and now falling, this is likely due to significant cell death, therefore not enough functioning cells to release ALT
63
When is the most common viral hepatitis causing ALF?
Hep E
64
When is Hep E particularly dangerous?
In pregnancEEEEEEEEE
65
What are the most dangerous risks/complications of ALF?
```
Cerebral oedema (causing raised ICP, particularly if concurrent renal failure or patient under 35))
Infection - in ALF, WCC drops (especially neutrophils), therefore susceptible to infection. (Give prophylactic antibiotics)
```
66
How does increased ammonia effect the brain?
Cause cerebral oedema
Brain acts as the alternative detoxification pathway, astrocytes convert ammonia --> glutamine. Excess glutamine has an osmotic effect and water is drawn into astrocytes (they swell), increasing water in the brain.
67
What is the treatment of cerebral oedema?
Bolus IV hypertonic saline
Aim to keep serum Na < 150 mmol/L
Cool patient
68
What is the definitive treatment for severe ALF?
Liver transplant
69
What is the difference between compensated and decompensated cirrhosis?
Compensated - no clinical signs/symptoms
Decompensated - Clinically evident complications
- Liver cell failure --> Coagulopathy, hyperproteinaemia, jaundice
- Portal HTN
70
Describe the process of cirrhosis formation (compensated)?
Stiff and scarred liver → increases intrahepatic vascular resistance →
In time develops an adaptive response with arterial vasodilatation in the Splanchnic circulation and an effective lower arterial blood volume →
Subsequent circulatory changes that initially can be regulated and compensated for.
71
Describe the process of cirrhosis formation (decompensated)?
Stiff and scarred liver → increases intrahepatic vascular resistance →
Develops an adaptive response with arterial vasodilatation in the Splanchnic circulation and an effective lower arterial blood volume →
As things become more severe, disease develops and portal pressure increases
Arterial vasodilatation in the splanchnic circulation becomes much more severe →
Arterial blood volume becomes greatly reduced → Changes in cardiac and renal circulation, due to secondary neurohumoral changes →
Develop sodium and water retention → ascites → hepato-renal failure.
72
What is decompensated cirrhosis? What can cause compensated cirrhosis to decompensate?
```
Deterioration in liver function in cirrhosis, that can manifest with the following:
• Jaundice,
• Increasing ascites,
• Hepatic encephalopathy,
• Renal impairment/hypovolaemia,
• Signs of sepsis
```
Decompensating events:
- Infection
- Constipation
- Increased alcohol
- Medication (opiates/NSAIDS)
- Dehydration
73
What is the natural history of cirrhosis, clinically?
Compensated cirrhosis → decompensating event → decompensated cirrhosis → If we can't reverse it then it can lead to hepato-renal failure, death and/or the requirement for liver transplant.
74
Why does cirrhosis increase cancer risk?
The cirrhosis cells are abnormal and therefore there is a greater risk of developing HCC (hepatocellular cancer).
75
What is the most common complication of cirrhosis?
Ascites
76
How does Ascites present?
Can often be found radiologically before clinically (USS)
Abdomen distension
Shifting dullness
77
What is the pathogenesis of ascites?
Cirrhosis (Scarred and stiff liver) → Increased intrahepatic vascular resistance & increased portal blood flow → portal hypertension → RAAS activation + ADH secretion → Na retention → Water retention →t Ascites
78
Why do we do ascitic fluid analysis?
1) measure neutrophil count to assess infection status.
- Neutrophil count > 250 cells/µL = SBP
2) measure SAAG (Serum ascites albumin gradient)
- SAAG = Albumin (serum) - Albumin (ascites)
- If >1.1g/L ascites due to portal HTN + cirrhosis (aka transudate, and not a rarer cause)
79
What is SAAG? What is its significance?
SAAG (Serum ascites albumin gradient)
- SAAG = Albumin (serum) - Albumin (ascites)
- If >1.1g/L ascites due to portal HTN + cirrhosis (& not a rarer cause)
80
What is the only definitive treatment for severe cirrhosis?
Liver transplant
81
What is SBP? How does it present (clinically and in lab tests)?
Spontaneous Bacterial Peritonitis
- Infection of the ascitic fluid in the absence of a secondary cause
Patients can present with fever and abdo pain
Ascitic analysis -
- Neutrophil count > 250 cells/µL = SBP
82
How do you treat SBP?
Abx ASAP --> IV co-amoxiclav or ciprofloxacin (oral)
83
What is Hepatorenal syndrome and how is it caused?
Large sodium retention leading to functional renal failure.
Occurs exclusively on the background of ascites (and usually hyponatraemia)
Due to marked hormonal and haemodynamic changes that occur in advanced portal hypertension
84
What are the 2 types of Hepatorenal syndrome?
Type 1 (acute) - secondary to precipitant
- Usually SBP, paracentesis, sepsis or GI bleed
- Rapidly progressive if untreated
Type 2 (chronic) - develops spontaneously
- usually in pts with diuretic resistance
- slower onset/progression
- median survival of 6 months without transplant
85
What is the treatment of Hepatorenal syndrome?
Terlipressin and albumin - combat spanchnic vasodilation
Stop nephrotoxic drugs - (NSAID, diuretics, etc.)
Liver transplant always gold standard
86
What are varices?
Essentially they are varicose veins that occur particularly in the oesophagus and the stomach.
87
What causes varices?
- Portal hypertension and vascular resistance lead to blood from the gut struggling to get through the liver and back to the heart and therefore it tries to find other routes.
- There are embryonic channels and areas of portal systemic anastomoses, particularly around the left/short gastric vein.
- Blood takes this route, collaterals develop, angiogenesis occurs and you develop these marked veins.
88
What is the risks of varices?
As pressure is high, it can cause spontaneous variceal bleeds.
89
How do we treat a patient with identified varices?
Primary prophylaxis
- Beta blockers (reduce BP)
- Nitrates
90
How do we treat acute variceal bleeds?
ABCDE (may need transfusion)
Endoscopic treatment.
- Tamponade with balloon
- Do every 2-4wks after until eradication
91
What secondary prophylaxis can we offer for recurrent variceal bleeds?
Telipressin (vasopressin analogue) currently best pharmalogical treatment.
Endoscopically tie off varies
TIPSS (artificial shunt to treat portal hypertension by allowing blood to bypass the liver)
92
What is Hepatic Encephalopathy (HE)?
Spectrum of neuropsychiatric abnormalities observed in patients with liver failure, due to an increase in gut-derived toxins in the blood
NB - in contrast to the HE from acute liver failure, cerebral oedema is a rare feature
93
What are the main causes of Hepatic Encephalopathy (HE)?
```
Infection
GI bleeding
Electrolyte disturbance
Constipation – This is a massive cause. Therefore make them poo loads.
Sedative drugs
```
94
What are the treatments of Hepatic Encephalopathy (HE)?
Treat underlying cause
Oral lactulose – aiming to prevent constipation, (2-3 stools/day) and decrease ammonia levels
Phosphate enemas
Rifaximin for persistent HE or >1 admission with HE
95
What are the clinical features of decompensated liver disease?
```
Jaundice – especially in the eyes
Finger clubbing
Gynacomastia
Spider naevi in SVC distribution
Hepatomegaly
```
96
Which blood tests indicate liver cell damage?
Increased ALT/AST indicate hepatocellular damage
97
Which tests indicate haemochromatosis?
Raised Ferritin & Transferrin saturation
98
Which tests indicate Wilson's disease?
Low caeruloplasmin & increased urinary copper
99
What type of virus if Hepatitis E and how is it transmitted?
RNA virus
| Faecal-oral transmission
100
When is hep E not self limiting and/or dangerous?
Dangerous in pregnancEEEEEEE (3rd trim)
Can cause chronic infection in immunocompromised pts
Can cause acute decompensation in cirrhotic patients
101
What extra-hepatic manifestations can hep e cause?
Neurological – (HEV found in CSF) – neuropathy & brachial neuritis (winged scapula), encephalitis, Guillain-Barre syndrome
Renal – Glomerulonephritis
Rheumatological – Arthralgia, myalgia, cryoglobulinaemia.
102
What are the zoonoses for Hep E? What is the implication of this?
Hep E strains found in pigs, deer and rodents.
| Therefore undercooked meat can spread disease.
103
What is the treatment of HEP E in immunocompromised patients?
Ribavirin
| also use if patient has fulminant hepatitis secondary to viral infection
104
How is Hepatitis B transmitted?
Blood bourne virus
- Perinatal (from mother to baby at birth)
- Unsafe injections and transfusions
- Sexual contact
- Child to child transmission
105
What type of virus if Hepatitis B?
The hepatitis B virus is a DNA virus belonging to the Hepadnaviridae family
106
Hep B serology.
| What does HBsAg positive indicate?
HBV infection
107
Hep B serology.
| What does HBV DNA levels indicate?
level of virus in the blood
108
Hep B serology.
| What does HBeAg positive indicate?
high level of HBV replication – usually high HBV DNA
| very infectious
109
Hep B serology.
| What does Anti-HBc IgM indicate?
suggests acute HBV
110
Hep B serology.
| What does Anti-HBc IgG indicate?
past or current HBV
111
Hep B serology.
| What does Anti-HBs Ab indicate?
vaccination or past infection
112
Hep B serology.
| What does Anti-HBe Ab indicate?
present in inactive HBV or the reactivation phase
113
What anti-viral's are available for the treatment of HEP B? What effects do they have on the liver?
Pegylated interferon Alpha2a
Entecavir - oral antiviral – Nucleotide/side analogues and stop viral replication
Tenofovir – oral antiviral - Nucleotide/side analogues and stop viral replication
Drugs dramatically reduce inflammation and can reverse liver fibrosis.
114
What is the aim of HBV therapies?
Stop progression of liver disease to prevent cirrhosis or HCC
HBsAg/Ab seroconversion = closest thing we have to a cure
Reduced HBsAg levels
Undetectable HBV DNA (although never completely cleared)
Normalisation of ALT
Histology – reduced inflammation and fibrosis
115
What type of virus if Hepatitis C?
Single-stranded RNA virus of the family Flaviviridae
116
How is Hepatitis C transmitted?
IV drug use (80% UK cases)
| Rarely - sexual contact
117
Who do we screen for HCV?
Any hx of injecting or intranasal drug use
ALT elevation
HIV or HBV infection, test for them all – you may as well.
Born in a highly endemic country
Long term dialysis
118
What are the new/best pharmalogical treatments of HCV?
```
DAAs – Direct Acting Antivirals - inhibit HCV viral replication
Protease inhibitors
• Telaprevir
• Boceprevir
• Simeprevir
• Parataprevir
Polymerase inhibitors (NS5B)
• Sofosbuvir
• Dasabuvir
NS5A inhibitor
• Ledipasvir
• Daclatasvir
• ombitasvir
```
119
Which drugs commonly cause liver injury?
Flucloxacillin, Clopidogrel and Co-amoxiclav both cause cholestatic patterns of liver injury
Paracetamol causes hepatocellular injury → Acute liver failure
HAART, NSAIDS and omeprazole also cause hepatocellular injury
Amitriptyline, phenytoin and trimethoprim cause a mixed picture
120
What is Budd-Chiari syndrome?
Occlusion of hepatic veins that drain the liver, which may cause acute liver failure
121
How is ascites treated?
Paracentesis - however this does not treat the underlying portal hypertension
122
What are the risk factors of TIPSS for varices?
Increased risk of hypoxic liver and transfer of toxins through the BBB
123
What cells are key in hepatic fibrosis pathogenesis?
Hepatic stellate cells - once activated they take up vitamin A and become myofibroblasts.
124
Which neurotransmitter has found to be involved in the fibrosis process (both regeneration and fibrosis?
Serotonin
5HT-2BR receptor - involved in fibrosis
5HT-2AR receptor - involved in regeneration
Therapies can antagonise the first receptor and agonise the second
125
What are the 4 ways in which liver responds to injury?
1. Resolution
2. Overwhelming injury, inadequate regeneration and massive necrosis
3. Suppuration and abscess formation
4. Progression to chronic inflammation and fibrosis
126
What are the two types of NAFLD?
1. Simple steatosis - fat without inflammation/injury
| 2. Non alcoholic steatohepatitis - fat with inflammation and cell injury
