Introduction to hepatology Flashcards
1
Q
Abnormal liver tests - acute
A
6 weeks
- Drugs
- Viral hep A, B, C, E
- Autoimmune hep
- Wilsons disease
2
Q
Abnormal liver tests - subacute
A
6-26 weeks
- Drugs
- Viral hep A, B, C
- Autoimmune hepatitis
- Wilsons disease
3
Q
Abnormal liver tests - chronic
A
> 26 weeks
- Viral hep B, C
- Alcohol
- NAFLD
- Autoimmune hepatitis
- Wilsons disease
- Hemochromatosis
- A1 antitrypsin deficiency
4
Q
Liver tests
A
- Bilirubin
- Liver enzymes
- Albumin
- Prothrombin time
- INR
5
Q
Liver enzymes
A
- Aspartate aminotransferase (AST)
- Alanine aminotransferase
- Alkaline phosphatase
- Gamma GT
- Albumin
6
Q
What is INR a measure of
A
- Measures extrinsic coagulation pathway. II, V, VII, X and fibrinogen
7
Q
Abnormal LFT’s - liver screen
A
Hepatitis serology - Hep A IgM, hep B surface antigen, hep C antibody, hep E IgG and IgM
- ANA, SMA LKM (for autoimmune hepatitis)
- AMA (for primary biliary cholangitis)
- Alpha 1 antitrypsin
- Copper, caeruloplasmin (Wilson’s disease)
- Ferritin (genetic haemachromatosis)
- Ultrasound
8
Q
What is raised in hepatitic damage
A
AST and ALT
9
Q
What is raised in cholestatic damage
A
Bilirubin and ALP
10
Q
Abnormal liver tests - hepatitic
A
- Viral hepatitis A, B, C, E
- Drug induced liver injury
- Autoimmune hepatitis
11
Q
Abnormal liver tests - cholestatic
A
- Biliary obstruction
- Viral hepatitis A, B, E
- DILI
- Autoimmune hepatitis
- Primary biliary cirrhosis cholangitis
- Primary sclerosing cholangitis
12
Q
What is the main feature of cirrhosis
A
- Increased pressure in the portal circulation, also known as portal hypertension
13
Q
Which readings have prognostic value
A
Bilirubin and PT/INR have prognostic value
14
Q
Features of acute liver failure
A
- No pre existing liver disease
- Coagulopathy
- Confusion (hepatic encephalopathy)
- Jaundice
- Abnormal liver tests
- Cerebral oedema
- Increased risk of infections
- Renal failure (hepatorenal syndrome)
15
Q
Causes of most cases of acute liver failure
A
- Indeterminate
16
Q
What causes a significant proportion of liver failure cases in the UK
A
- Paracetamol overdose
17
Q
Recommended dose of paracetamol per day
A
- 4gms/day
- toxic dose > 15 gms
- Lower toxic dose if pre existing liver disease, alcohol excess
18
Q
Metabolism of paracetamol
A
1) Glucuronidation
2) Sulfation
3) N-hydroxylation and dehydration, then glutathione conjugation, (less than 15%). The hepatic cytochrome P450 enzyme system metabolises paracetamol (mainly CYP2E1), forming a minor yet significant alkylating metabolite known as NAPQI (N-acetyl-p-benzoquinone imine) (also known as N-acetylimidoquinone) NAPQI is then irreversibly conjugated with the sulfhydryl groups of glutathione
19
Q
NAPQI
A
- Toxic reactions with proteins and nucleic acids
20
Q
How does NAC help with paracetamol overdose
A
- N acetyl cysteine (NAC) replenishes glutathione which conjugates with NAPQI and detoxifies it
21
Q
How does paracetamol overdose present
A
- Presents with nausea, vomiting, RUQ pain, confusion
- Jaundice and liver failure usually develops after 3-4 days
- Very high liver enzymes and prothrombin time
22
Q
Paracetamol overdose - prognosis
A
- If receive N acetyl cysteine within 16 hours liver failure rare
- Some benefit of NAC even up to 36 hrs
- In severe cases liver transplant only option
23
Q
Features of cirrhosis
A
Portal hypertension
- Varices
- Ascites
- Hepatic encephalopathy
- Jaundice
- Spiders
- Enlarged spleen/pancytopenis
- Renal failure (HRS)
- Hepatocellular cancer
24
Q
Ascites management in cirrhosis
A
- Salt restriction
- Fluid restriction if low sodium
- Diuretics (spironolactone and furosemide)
- Large volume paracentesis(LVP) with albumin cover
If refractory ascites - recurrent LVP
- Transjugular intrahepatic portosystemic shunt
- Consider liver transplant
- Long-term drains(if palliative) - still undergoing research
25
Variceal bleed
- Haemodynamically stable, correct coagulopathy and thrombocytopenia
- IV terlipressin and IV antibiotics
- Endoscopy in theatre with an anaesthetist present - variceal banding
- If blood bath - balloon tamponade
- Non selective B blockers for secondary prophylaxis(propanolol and carvedilol)
26
Hepatorenal syndrome (AKI)
- 'Functional' and fairly rapid renal impairment due to reduced renal perfusion
- Increase in serum creatinine by 50% from baseline within 3 months
- Type 1 and 2
- Treat underlying cause, terlipressin
- Liver transplant
27
Hepatic encephalopathy
- Elevated ammonia
- Diagnosis of exclusion
- Treat precipitating cause - constipation, diuretics, infection, sedatives, GI bleed
- Lactulose
- Non absorbable antibiotics (rifaximin)
28
Types of liver failure
A - compensated cirrhosis
B - Compensated cirrhosis ---> hepatic and extrahepatic organ failure
C - Compensated cirrhosis --jaundice, ascites, variceal bleeding, hepatic encephalopathy--> decompensated cirrhosis
29
Severe alcoholic hepatitis
- Most serious form of alcohol related injury
- Characterised by jaundice and coagulopathy
- In patient untreated mortality - 40%
- Various prognostic scores(discrimant function)
- Steroids and pentoxyfilline
30
Hep C virus risk factors
- Recipients of clotting factors made before 1987
- Injection drug use
- Long-term hemodialysis
- Individuals with multiple sex partners
31
Precipitants to chronic liver failure
- Viruses
- Drugs
- Alcohol
- Ischaemia
- Surgery
- Sepsis
- Idiopathies
32
Factors associated with disease progression
- Alcohol consumption
- Disease acquisition at>40 years
- Male gender
- HIV coinfection
- Hep B virus coinfection
- Immunosuppression
33
Hep C natural history
- Normal liver --> acute infection --> chronic infection develops in 80% --> chronic hepatitis --> cirrhosis develops in 20% --> risk --> risk of carcinoma, 1-4% per year
<20 years
34
Non-alcoholic fatty liver disease
- Resemble alcoholic liver disease but occur in absence of alcohol abuse
- Usually associated with metabolic syndrome - type 2 dm, obesity, HTN, and elevated TG
- Underlying mechanism is insulin resistance (IR)
35
Indications for liver transplant in acute liver failure - with paracetamol usage
- pH<7.3 after fluid resucitations or
- Arterial lactate>3.5mmol at 4 hrs or
- Arterial lactate > 3.0 mmol/L at 12 hrs or
- PT>100 secs(INR>6.5), serum creatinine>300 mmol/l (3.4 mg/dl) grade 3 or 4 encephalopathy
36
Indications for liver transplant in acute liver failure - non paracetamol
- Prothrombin time greater than 100 secs (INR?6.5) (irrespective of grade of encephalopathy) or any three of the following
1. Age less than 11 years or greater than 40 years
2. Etiology of non-A/non-B hepatitis, halothane hepatitis, or idiosyncratic drug reactions
3. Duration of jaundice of more than 7 days before onset of encephalopathy
4. Prothrombin time greater than 50 secs (INR>3.5)
5. Serum bilirubin level greater than 17 mg/dL (300 micromol/l)
37
Indications for liver transplant in cirrhosis
- Ascites/SBP
- Variceal bleeding
- Hepatic encephalopathy
- Hepatocellular cancer
38
Prognostic scores to prioritise liver transplant in cirrhosis
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MELD and UKELD score:
Bilirubin
INR
Creatinine
Na
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