Hepatology Flashcards
Wilson disease
a) Gene, chromosome and inheritance
b) Treatment
c) Renal disease associated
d) Screening test
e) When is liver biopsy needed?
f) Neurological involvement
a) ATP7B gene on Chromosome 13 (Wilson disease has 13 letters)
- Autosomal recessive inheritance
- Leads to inadequate hepatic synthesis of ceruloplasmin
- This leads to increased free copper which deposits in various tissues
b) Treatment:
- Penicillamine (copper chelator)
c) Renal tubular acidosis type 2 (proximal)
- Fanconi-like syndrome
- Failure to reabsorb bicarb
- Hypophosphataemia, hypokalaemia
d) - Low serum ceruloplasmin (95% sensitivity)
- In presence of Kayser-Fleischer rings, this is diagnostic
- Urinary copper excretion increased
- Most have low serum copper
e) If no Kayser-Fleischer rings/neurological abnormalities or normal ceruloplasmin
f) Parkinsonism, dysarthria, involuntary movements, dementia
Autoimmune hepatitis
a) 2 types
b) Antibodies associated with each
c) Bloods
d) Presentation
e) Management
a) Type 1 - associated with other AI conditions (e.g. PA, thyroid, etc.), ANA and anti-SMA +/- p-ANCA
b) Type 2 - young women, anti-liver/kidney microsomal (anti-LKM*) antibodies; generally more severe, more rapid onset and less responsive to steroids
*Anti-LKM2 antibodies may be raised in drug-induced hepatitis. Liver biopsy may be needed to differentiate between the two conditions
c) - Raised IgG
(as opposed to PBC which causes raised IgM)
- ALT high, with ALT: AST ratio >2:1
(as opposed to PBC/PSC which cause more ALP rise)
d) - May have insidious onset of cirrhosis
- May have rapid onset of RUQ pain, jaundice and hepatosplenomegaly with acute liver failure
(as opposed to PBC/PSC which tend to present with pruritis)
e) - Prednisolone, then steroid-sparing agents
(generally indicated if ALT >10x upper limit of normal)
- If these fail, liver transplant
Budd-Chiari syndrome
a) Causes
b) Presentation
c) Management
a) Hepatic vein thrombosis, increased risk with hypercoagulable state:
- Inherited thrombophilias
- COCP
- Malignancy
b) Acute ascites, tender hepatomegaly, splenomegaly, other signs of CLD
c) - Anticoagulation
- Venous shunting (TIPS)
- Liver transplant if needed
PBC vs PSC
PBC
- Intrahepatic
- females, RA/Sjogren’s/CREST
- presents with itching and malaise, or cirrhotic fx/UGIB, or xanthelasma
- 98% have +AMA, also IgM (vs IgG in autoimmune hepatitis)
- Associated with HCC
- Liver biopsy: portal hepatitis, with granulomatous destruction of bile ducts
- Rx: UDCA for itching. Liver transplant only definitive treatment
PSC
- intra- and/or extra-hepatic
- males, 90% have IBD
- may have systemic features (e.g. fevers, night sweats, weight loss)
- ANA, p-ANCA, SMA
- Associated with cholangiocarcinoma and colorectal Ca
- MRCP: multiple beaded biliary strictures
- Liver biopsy: fibrous obliterative cholangitis with loss of interlobular and septal bile ducts with ‘Onion Skin’ appearance
Rx: liver transplant only definitive treatment
Both cause predominantly cholestatic picture on LFTs (raised ALP)
Drug-induced hepatitis
a) Acute culprits
b) Chronic culprits
c) Antibody
d) Which drugs tend to cause predominantly cholestatic picture?
a) - Paracetamol, NSAIDs
- Anticonvulsants, anti-rheumatic drugs (especially MTX)
- Anti-TB drugs
- Macrolides
- Co-amoxiclav (often delayed by a few weeks)
- Anabolic steroids
- Statins
b) Ketoconazole, isoniazid, methyldopa, nitrofurantoin
c) Anti-LKM2
d) - Co-amoxiclav
- Carbamazepine
Hydatid disease
a) Cause and risk factors
b) Presentation
c) Investigations and findings
d) Management
a) Echinococcus granulosis (from dog tapeworm) - causes cyst formation
- risk in sheep farmers
b) RUQ pain, weight loss, night sweats
- May present with cysts elsewhere (e.g. lungs - SOB, brain - raised ICP, focal neurology)
c) Liver US - cysts
LFT derangement
Eosinophilia
d) Surgery +/- albendazole
Serum-ascites albumin gradient
a) Calculation
b) Differentials
a) Serum albumin - ascites albumin (difference not ratio)
b) High gradient = portal hypertension (cirrhosis, Budd-Chiari, obstruction, CCF)
Low gradient = not portal hypertension
- High protein - pancreatitis, cancer, TB
- Low protein - nephrotic syndrome
Haemochromatosis
a) Inheritance and common mutation
b) Presentation
c) Investigations
d) Treatment
a) - HFE gene (mnemonic: Haemochromatosis Fe for iron) on chromosome 6 (haemochromato-six)
- Types 1-3 autosomal recessive
- Most common mutation is C282Y
- Also common is H63D
b) Men: symptoms start in 40s usually
Women: onset usually after menopause
- Abnormal LFTs, hyperferritinaemia
- Skin - bronzing, porphyria cutanea tarda (check urine - tea coloured)
- Heart - cardiomyopathy, arrhythmias, heart failure
- Diabetes
- Neuropsychiatric - memory, irritability, mood labile
- Hypogonadism (due to pituitary deposits)
c) - Serum iron, ferritin, TSAT* and TIBC
- LFTs, CRP
- Genetic testing for C282Y and H63D
- If ferritin >1000, proceed to liver biopsy
- If ferritin <1000, risk of liver cirrhosis <1% (no need for liver biopsy)
*Transferrin saturation (TSAT) is the best indicator of iron overload (TSAT >55%)
TSAT (same as iron saturations) is calculated as serum iron divided by TIBC
TIBC will be low-normal in haemochromatosis
d) Venesection:
- 400-500 ml of blood (200-250 mg iron) weekly or every two weeks.
- Adequate hydration before and after treatment and avoidance of vigorous physical activity for 24 hours after phlebotomy are recommended
- Cardiomyopathy tends to improve with venesection
- Aim is to reduce TSAT <50% and ferritin <50
If venesection contraindicated:
- Desferrioxamine (iron chelator)
Other:
- Diuretics for heart failure
- Diabetic control
- Liver transplantation
TIPS
a) Indications
b) Contraindications
a) Emergency TIPS - for patients with variceal bleeding resistant to banding and beta-blockers
Elective TIPS:
- For refractory ascites
- For secondary prevention of varices resistant to medical therapy
- For Budd-Chiari resistant to anticoagulation
- For portal vein thrombosis
b) - Encephalopathy (may worsen or precipitate)
- Child Pugh C >10, or MELD >18
- Severe LVSD
- CKD 4 or higher
- Caution in age >65 due to risk of encephalopathy
Antibody/antigen tests for hepatitis.
a) Hep A - acute? - past infection/immunity?
b) Hep B - acute? - chronic? - past infection? -infectious? - vaccination?
c) Hep C - acute? - chronic? - cleared infection?
a) - Acute - IgM Hep A antibody (from ~ 3 weeks)
- Immunity/past infection - IgG Hep A antibody
b) - Acute - Hep B surface ANTIGEN (HBsAg)
- Chronic - HBsAg > 6 months
- Past infection - Hep B CORE ANTIBODY
- Infectious - Hep B ‘e’ antigen (HBe Ag), also high risk of HCC and chronic disease
- Vaccination - Hep B SURFACE ANTIBODY (immunity)
c) - Acute - serum HCV RNA
- Chronic: serum HCV antibody (takes ~ 3 months to appear)
- Cleared infection: Anti-HCV IgG present but undetectable HCV RNA viral load (occurs in 30% HCV infections)
Encephalopathy grading
Grade 1: change in behaviour with minimal change in consciousness
Grade 2: Disorientation, drowsiness, liver flap, inappropriate behaviour
Grade 3: Marked confusion, incoherent speech, sleeping most of the time but rousable to voice
Grade 4: Comatose, unresponsive to pain; decorticate or decerebrate posturing
Paracetamol overdose.
a) Indications for transplant
b) Poor prognostic factors (not part of transplant criteria)
c) Recurrence of N&V after 2-3 days usually indicates what?
d) When is liver damage maximal?
e) When should paracetamol levels be taken?
f) When can paracetamol levels not be reliably used?
a) King’s College Criteria:
- Arterial pH < 7.30 after fluid resus, or
- INR >6.5 (PT >100) AND Creatinine >300 AND grade III/IV encephalopathy
Note- don’t need all these criteria at the same time
b) - Lactate >3 after fluid resuscitation
- Phosphate >1.2 at 24 hours
c) Hepatic necrosis
d) 3-4 days post ingestion
e) At least 4h post-ingestion
f) - Presenting >24h post-ingestion
- Treat if any of RUQ pain, N&V, raised ALT, raised INR (irrespective of paracetamol level)
- Beware little old dears taking unintentional therapeutic overdose (staggered) for their arthritis
Treatment of paracetamol OD.
a) Non-staggered overdose (tablets ingested over period < 1 hour) - indications for charcoal, indications for NAC*
b) Reasons to stop NAC
c) Therapeutic excess - define, treatment
d) Staggered overdose - define, treatment
e) NAC dosing
f) How do the above treatment thresholds differ in “high risk” patients, and what does high risk mean?
g) How NAC works
- Consider presentation time:
- Within 1 hour
- Within 8 hours
- 8-24 hours
- > 24h
a) If presenting within 1 hour of ingestion, and ingested >150mg/kg, consider activated charcoal.
Give NAC for any of the following:
- Presenting within 8 hours with paracetamol level on or above treatment line
- Presenting between 8-24 hours if ingestion of >150mg/kg OR, if paracetamol level on or above treatment line
- Presenting >24h post ingestion if any of… RUQ tenderness, jaundice, INR >1.3 or ALT above ULN (unless chronic)*
*If any of these present, treat even if paracetamol level < treatment line
b) If NAC started due to ingestion >150mg/kg before bloods taken, can subsequently stop NAC if all following are present:
- Paracetamol level < treatment line
- Normal ALT
- INR 1.3 or less
- Patient is asymptomatic
c) Therapeutic XS:
- Intent to treat pain/fever with excess in 24h period
- Low risk of toxicity 75-150mg/kg (10-20 in 24h for me) and high risk >150mg/kg (>20 in 24h for me)
- If >75mg/kg in 24h or >4g/day for 2 days, take paracetamol level, U&E, INR, bicarbonate 4 hours after last paracetamol tablet
- If the above results are normal and patient is asymptomatic, discharge
- If any abnormality/symptoms, treat with NAC as for staggered OD
- Treatment threshold lower in high risk groups*
d) Staggered OD:
- Ingestion of intentional OD with tablets taken over >1 hour
- Treat urgently with NAC
- Take bloods 4h after last ingested tablet for paracetamol level, LFT, U&E, INR and bicarb
- If above normal, can discontinue NAC
- Note: still need assessment by MHLT
e) 21 hour regimen:
- 150mg/kg over 1 hour
- 50mg/kg over 4 hours
- 100mg/kg over 16 hours
f) *High risk groups:
- >recommended units alcohol per week
- regular use of enzyme inducing drugs
- depleted glutathione stores (HIV, malnutrition, cirrhosis)
Generally 75mg/kg is used as dangerous threshold rather than 150mg/kg in low risk groups
g) Paracetamol toxicity causes toxic accumulation of metabolite NAQPI, which is cleared by glutathione. NAC replenishes glutathione stores
ALD vs NAFLD
- LFTs
ALD: AST > 2x ALT
NAFLD: ALT > 2x AST
Why is lactulose useful for chronic liver disease?
Leads to reduction in ammonia absorption in gut
- reduced encephalopathy
