Hepatology Flashcards
Give 2 causes of an isolated rise in unconjugated bilirubin?
Gilbert’s syndrome and haemolysis
What are the 5 f’s associated with gallstones?
Female, fat, forty, fair and fertile.
list 4 causes of acute pancreatitis
GET SMASHED Gallstones Ethanol (alcohol) Trauma Steroids Mumps/Malignancy Autoimmune Scorpion venom Hyperlipidaemia, hypothermia, hypercalcaemia ERCP and emboli Drugs
give 3 symptoms/signs of acute pancreatitis
pain, nausea, vomiting. tachycardia, fever, jaundice, shock, ileus, rigid abdomen ± local tenderness. Cullen’s and Grey Turner’s signs.
what investigations would you carry out in acute pancreatitis?
FBC, CRP, U&Es (including glucose, calcium, albumin), LFTs, ABG, amylase/lipase (usually 3x upper limit)
Imaging = Erect AXR, Abdo USS, CT abdo with contrast
Give 3 criteria in the Modified Glasgow criteria for predicting severity of pancreatitis
PANCREAS = PaO2 <8.0kPa, Age >55 years, Neutrophils (>15 x 10^9/L), Calcium <2 mmol/L, Renal function, Enzymes (AST, LDH), Albumin <32g/L, Sugar (gluc >10mmol/L)
Outline the medical management of acute pancreatitis?
- Admit, NBM, may need NG
- O2, aggressive IV fluids, analgesia, anti-emetics
- Fluid balance
- VTE prophylaxis
- Glucose measured
- Enteral if prolonged fasting. May need ITU
Give 2 early and 2 late possible complications of acute pancreatitis
Early: shock, ARDS, renal failure, DIC, hypocalcaemia.
Late: pancreatic necrosis, abscesses, bleeding, pseudocyst
What is chronic pancreatitis?
Chronic inflammation of pancreas with progressive destruction of the exocrine pancreas, resulting in irreversible injury
3 causes of chronic pancreatitis?
Alcohol (80%), idiopathic, genetic (CF), autoimmune, malnutrition, pancreatic duct obstruction
Give 4 clinical features of chronic pancreatitis
Intermittent abdo pain radiating to back
N/V
Malabsorption Sx e.g. steatorrhoea, diarrhoea, weight loss
Glycaemic dysfunction
First line imaging for chronic pancreatitis and what alternatives if CI?
CT pancreas with contrast
MRCP or EUS
What 2 markers can be used to assess pancreatic function in chronic pancreatitis?
Serum glucose (raised if endocrine insufficiency) Faecal elastase (reduced)
Management of chronic pancreatitis?
NSAIDs for abdo pain (may need opioids)
Creon + fat-soluble vit supplements.
No alcohol, low fat diet.
Glycaemic control
Describe the 3 different types of gallstones and their causes
Cholesterol stones - large, radio-opaque - age, obesity, female sex.
Pigment stones - small, friable, irregular - haemolysis. Black pigment stones are radio-opaque, brown are radio-lucent.
Mixed stones - faceted (calcium salts, pigment and cholesterol).
3 investigations for gall stones?
LFTs - bilirubin, ALP, GGT may be raised
Abdo US
consider MRCP
Management options for gall stones?
Dietary advice
Reassurance if asymptomatic
Lap chole if symptomatic
CBD stones–> ERCP for clearance, then lap chole
How does acute cholecystitis develop from an obstruction?
Obstruction to gall bladder emptying - bile retention - distension and inflammatory response to retained bile
What are 2 causes of acalculous cholecystitis?
Biliary stasis due to sepsis, trauma or extrinsic compression
Biliary sludge
What special test would you do on examination to confirm cholecystitis?
Murphy’s sign - 2 fingers over RUQ + ask patient to breathe in - causes pain and arrest of inspiration as inflamed gallbladder hits your fingers
Needs to be negative on left side in order for Murphy’s to be positive
how would you differentiate the pain of biliary colic from cholecystitis?
cholecystitis features an inflammatory component - local peritonism, fever, high WCC
5 investigations to do in acute cholecystitis?
FBC (raised WCC), CRP (raised), LFTs , amylase to rule out concurrent pancreatitis Abdo US CT abdo (if empyema or perforation suspected)
Management of cholecystitis?
- Opioids and anti-emetics
- IV fluids and antibiotics
- Lap chole, most after 6-12 weeks once settled, or can be immediate.
A patient presents with jaundice, RUQ pain and fever. What does this presentation suggest?
Charcot’s triad –> ascending cholangitis
What is Reynolds pentad for cholangitis?
Charcot’s triad (RUQ pain, jaundice, fever) plus altered mental state and hypotension
4 common causative organisms of cholangitis?
Klebsiella spp., E.coli, enterococci and streptococci
What is the most common underlying pathology in ascending cholangitis?
Bile stasis due to obstructing CBD stone
Management of cholangitis?
- Initial resus e.g. IV fluids, oxygenation
- IV abx (based on local policy) following blood cultures
- ERCP (stone removal +/- sphincterotomy +/- stenting
Give 3 conditions assoc with cholangiocarcinoma
How is it diagnosed?
Serum marker?
Management?
PSC, infections with liver flukes, gallstone disease, Caroli disease.
Dx on imaging e.g. CT or MRCP
CA 19-9 may be elevated
Surgery is mainstay
give 3 causes of unconjugated hyperbilirubinaemia (pre-hepatic jaundice)
Haemolysis - malaria, DIC, haemolytic anaemia
Ineffective erythropoiesis.
Impaired hepatic uptake - drugs (contrast agents, rifampicin), RHF.
Impaired conjugation - Gilbert’s syndrome, Crigler-Najjar.
what will the urine and faeces look like in conjugated hyperbilirubinaemia (hepatic/post-hepatic jaundice)? why?
urine = dark - conjugated bilirubin is soluble, so excreted in urine. Faeces = pale - less conjugated bilirubin enters gut.
Give 5 hepatic causes of jaundice
Hepatitis - viral, autoimmune, alcoholic
Drugs - paracetamol, statins, rifampicin, isoniazid, ketoconazole
Carcinoma
Hereditary - haemochromatosis, Wilson dis, A1AT def
Give 3 causes of obstructive/cholestatic jaundice?
Gall stones, pancreatic cancer, cholangiocarcinoma, PSC, PBC,
Drugs e.g. fluclox, co-amox, sulphonylureas, COCP
How is hepatitis A spread? what are the risk factors?
Faecal-oral route. Poor sanitation, overcrowding, contaminated food/water.
What serological marker indicates acute Hep A infection?
What indicates immunity/past infection?
Anti-HAV IgM
Anti-HAV IgG
How do you manage Hep A?
Supportive, self-limiting
Most of the viral hepatitis A-E are RNA viruses, apart from which one?
Hep B is a DNA virus
Which hepatitis virus is dependent on Hep B infection for replication?
Hep D - it’s an incomplete RNA virus and needs concurrent hep B infection
Most common cause of hepatitis?
Hep B
How is hep B spread?
Blood-borne (IVDUs, vertical, needle-stick injury) and sexual transmission
What serological marker indicates acute infection of Hep B?
Hep B is deemed chronic if this marker persists for how long?
HepB surface antigen
6 months
HBV surface antigen antibody indicates what two possibilities regarding infection?
Implies immunity - either past exposure or vaccination
What serological marker can help determine whether Hep B immunity comes from past infection or vaccination?
Anti-HBc - indicates current or past infection
c = caught, so negative if immunised
Which of hepatitis A-E have a vaccine?
A, B (and so D)
What drugs are indicated in management of chronic hep B?
PEGinterferon +/- antivirals (tenofivir, entecavir)
2 possible comps of Hep B?
Cirrhosis, HCC, cholangiocarcinoma, chronic hepatitis, fulminant liver failure, polyarteritis nodosa
How is hep C transmitted?
Blood, sexual
The presence of what 2 serological markers indicate active hep C infection?
HCV RNA and anti-HCV
Management for chronic hep C?
PEGinterferon +/- ribavirin +/- antivirals
What % of acute hep C develops to chronic?
60-80% , so the majority!
Who cannot be prescribed ribavirin?
Pregnant women, it’s very teratogenic.
Women shouldn’t get pregnant within 6 months of stopping ribavirin.
4 comps of chornic hep C?
HCC, cirrhosis, cryoglobulinaemia, arthritis, Sjogren’s
How is Hep E transmitted?
Faeco-oral, main reservoir in pigs
What serological marker indicates active Hep E infection?
HEV antibody (Anti-HEV IgM)
What collagen type is deposited in the liver in cirrhosis?
Type 1 and 3
If there was alpha-fetoprotein present in the serum of a cirrhosis patient, what would you suspect to be the cause of their cirrhosis?
HCC
5 causes of cirrhosis?
Alcoholic liver disease, Hep B/C, NAFLD, autoimmune (PSC, PBC), hereditary conditions (Wilson, haemochormatosis)
What grading system is used to assess the severity of chronic liver disease?
What are the components
Child-Pugh - ABCDE
Albumin Bilirubin Clotting (PT) Distension (ascites) Encephalopathy
3 clinical features of liver failure
pruritus, jaundice, raised LFTs, leuconchyia, Terry’s nails, clubbing, palmar erythema, hyperdynamic circulation, Dupuytren’s, spider naevia, xanthelasma, gynaecomastia, atrophic testes, loss of body hair, parotid enlargement, hepatomegaly
What investigation confirms diagnosis of cirrhosis?
Liver biopsy
What is considered portal hypertension?
What is the most common cause of portal HTN?
> 12mmHg
Cirrhosis
TIPS shunt involves placing a stent between which two vessels?
Hepatic vein and portal vein
What are 3 absolute contraindications for liver transplant?
Extrahepatic malignancy, severe extrahepatic disease, systemic sepsis, untreated HIV infection, ongoing alcohol use, active illicit drug use
What’s the difference between hyperacute and acute transplant rejection?
Hyperacute - due to ABO incompatibility.
Acute - T cell mediated, 5-10d post-op, patient feels unwell with pyrexia and tender hepatomegaly - managed by altering immunosuppressives
What is the likely pathophysiology of hepatic encephalopathy?
Excess absorption of ammonia and glutamine
How is hepatic encephalopathy managed?
Treat any electrolyte disturbances, dehydration, infection.
Clear endotoxins - lactulose
Abx prophylaxis - rifaximin
What measurement can determine the cause of ascites?
Serum-ascites albumin gradient
What is classed as a high SAAG?
What causes ascites with high SAAG?
> 1.1g/dL
Portal hypertension e.g. cirrhosis, heart failure, Budd-Chiari syndrome, constrictive pericarditis
What is a low SAAG?
What causes ascites with low SAAG?
<1.1g/dL
Nephrotic syndrome, malignancy, pancreatitis, TB
Management of ascities?
- Salt restricted diet
- Spironolactone first-line, otherwise furosemide
- Some may benefit from therapeutic paracentesis
What is the commonest causative organism in spontaneous bacterial peritonitis?
E coli
What is diagnostic of SBP?
Management?
Ascitic tap –> polymorph/neutrophil count >250x10^6/L
IV broad-spec Abx, albumin replacement
What changes would you see on a liver biopsy of an alcoholic hepatitis patient?
Fatty change and infiltration by polymorphonuclear leucocytes and hepatocytes in zone 3. Mallory bodies - dense cytoplasm and giant mitochondria.
What is the path of damage the alcoholic liver follows?
Fatty liver (steatosis) - alcoholic hepatitis - fibrosis - micronodular cirrhosis
Outline the management of alcoholic hepatitis?
- Alcoholic cessation and benzos for withdrawal
- Vit B1 replacement (Pabrinex), then PO thiamine
- Nutritional supplementation
What is the classic triad of Wernicke’s encephalopathy?
What causes Wernicke’s?
Confusion, ataxia, ophthalmoplegia (nystagmus, lateral rectus palsy)
Long-standing thiamine (B1) deficiency
What symptoms indicate Korsakoff’s syndrome?
Anterograde and retrograde amnesia
Confabulation
What is NAFLD?
What is the two hit hypothesis?
Excess of fat accumulating in the liver, in absence of excessive alcohol consumption.
First hit = insulin resistance responsible for fatty acid deposition in liver. Hepatic steatosis
Second hit = further oxidative stress –> inflammation. Steatohepatitis
What index should be calculate to diagnose NAFLD?
What components make up this index?
Fatty liver index (FLI): weight, height, waist circumference, serum GGT, triglyceride
Diagnose if FLI >60
What is the gold standard investigation for NAFLD?
2 other investigations?
Liver biopsy
LFTs, Liver US, enhanced liver fibrosis (ELF) testing
Managment of NAFLD?
- Lifestyle advice e.g. diet, exercise, alc
- RF reduction e.g. BP and gylcaemic control
- Pioglitazone in pt with advanced fibrosis
What is the pathophysiology of hereditary haemochromatosis (HHC)?
AR inheritance with a mutation in the HFE gene (chromosome 6). Causes reduced production of hepcidin, which regulates iron absorption in the gut. This increases gut absorption of iron, leading to excess iron in multiple organ systems.
List 3 clinical features of HHC?
More common in M or F?
Bronze complexion, hepatomegaly, cirrhosis, dilated cardiomyopathy, osteoporosis, diabetes mellitus, hypogonadism, mood disturbance, cognitive impairment
More common in M. Present at age 40-60.
What would be the iron studies test results (transferrin saturation, ferritin, total iron binding capacity) in HHC?
Raised transferrin saturation, ferritin raised, TIBC lowered
Other thn iron studies, what Ix would you do for HHC?
LFTs, ECG, Liver MRI +/- biopsy
Offer HFE genetic testing
What staining on liver biopsy for HHC?
Perl’s staining
What is first line treatment of HHC?
What is second line?
Other considerations?
Venesection - once a week, then a few times a year.
Desferrioxamine (iron chelator) if can’t venesect.
Low iron diet
Screen family members.
Liver transplant if end stage disease
What is Wilson disease?
AR disorder resulting in impaired excretion of copper in bile and faeces, leading to toxic accumulation of copper
Give 4 clinical features of Wilson disease, in 4 different organ systems.
Liver- acute liver injury, cirrhosis, liver failure Eyes- Kayser Fleischer rings Neuro- ataxia, tremor, dyskinesia Psych- depression, psychosis, dementia Rheum- arthritis, osteopenia
Give 2 investigations and results for Wilson disease
Serum caeruloplasmin (metabolite of copper) = reduced 24 hr urinary copper excretion = >100mcg suggestive Slit lamp = Kayser-Fleischer rings
What is the treatment of Wilson disease?
Lifelong penicillamine (trientine is alternative) May need liver transplant
What is alpha1-antitrypsin?
Glycoprotein protease inhibitor that controls the inflammatory cascade. Synthesised in the liver and protects lung tissue from damage by elastase.
What is the pathophys of A1AT deficiency?
Autosomal co-dominant genetic disorder caused by mutations on Ch 14. Defective forms of A1AT can’t be exported out of liver–> congestion, apoptosis and liver failure. Lack of A1AT –> uncontrolled elastin breakdown, emphysema
2 ways A1AT deficiency might present?
Dyspnoea, wheeze. Or deranged LFTs, cirrhosis.
4 investigations and their results for A1AT def
Serum A1AT - low <10umol/L Spirometry - obstructive picture CXR - may show emphysema Genotyping Liver biopsy
What staining is used for liver biopsy in A1AT deficiency and what does it show?
Periodic Acid Schiff = PAS + globules
Outline management of A1AT deficiency
- Lifestyle advice e.g. stop smoking, alc cessation
- Manage emphysema as per COPD
- HCC surveillance and liver transplant for advanced disease
What is the pathophys of autoimmune hepatitis?
Environment trigger e.g. virus, sets off inflammatory cascade in immunogenetically susceptible patients
AIH is more common in M/F? What age does it affect most?
F. Bimodal age distribution- first peak in 20s, second peri/postmenopausal.
Which 2 antibodies are usually present in AIH?
Anti-nuclear antibody and anti-smooth muscle antibody
Other than auto-antibodies, 3 other investigations for AIH?
Protein electrophoresis - may have high IgG titres
LFTs - hepatitic picture
Liver biopsy
Management of:
a) asymptomatic, pre-cirrhotic AIH
b) acute episode of AIH
c) very advanced AIH
a) watchful waiting
b) 40mg prednisolone, tapered over weeks
c) Liver transplant
Describe the underlying pathogenesis of primary biliary cirrhosis?
Serum antimitochondrial antibodies (AMA) cause chronic inflammation of intrahepatic bile ducts causing cholestasis, cirrhosis and portal hypertension.
2 assoc conditions of PBC?
Is it more common in M/F?
Coeliac, thyroid disease, systemic sclerosis
F
What picture is seen on LFTs in PBC?
Predominantly cholestatic (high ALP and GGT) but ALT/AST may be raised
Give 4 clinical features of PBC
- Fatigue and pruritus earliest symptoms
- Jaundice (late)
- Hepatosplenomegaly
- Xanthelasmas
Other than LFTs, what two blood tests are used to diagnose PBC?
What further investigation would you do?
AMA
High levels of IgM
Imaging - USS
How would you treat primary biliary cirrhosis?
Ursodeoxycholic acid.
Fat soluble vitamin supplements for malabsorption. Bisphosphonates and calcium supplements for osteoporosis,
Cholestyramine/rifampicin for pruritus
May need liver transplant
A 38 year old man presents to the GP complaining of intermittent jaundice and pruritus, and fatigue. He has UC which is currently well controlled. His LFTs reveal a cholestatic picture.
What is the likely diagnosis?
What is the pathophysiology?
Primary sclerosing cholangitis
Chronic inflammatory changes of extrahepatic and/or intrahepatic bile ducts results in biliary fibrosis and stricture formation. Causes cholestasis and predisposes to cholangitis. Eventually causes cirrhosis
Other than LFTs, what 2 investigations and results for PSC?
pANCA present in 60%
MRCP for visualising intra and extrahepatic ducts
Management of PSC?
- Cholestyramine
- Ursodeoxycholic acid
- Prophylactic Abx
- Liver transplant for end stage
What is Budd-Chiari and what are 3 causes?
Hepatic outflow obstruction
Assoc with hypercoagulable states e.g. PRV, factor V Leiden, Protein C/S deficiency, Athiphospholipid syndrome, COCP, HRT, pregnancy, surgery,
What is the triad of features seen in Budd-Chiari?
Abdo pain - sudden onset, severe
Ascites
Tender hepatomegaly
What investigation is sensitive for Budd-Chiari?
US with Doppler flow studies
Management of Budd-Chiari
- Thrombolysis if clot visualised e.g. alteplase
- Lifelong anticoagulation
- manage ascites
- Consider TIPSS and liver transplant
A patient with known cirrhosis presents with decompensated symptoms and worsening LFTs. He has RUQ pain and hepatomegaly, and notes he has lost 10kg weight in the last 3 months. What is the likely diagnosis?
Give 3 investigations to help diagnose this?
Hepatocellular carcinoma
Liver US
CT CAP for distant mets
Liver MRI if diagnostic uncertainty
AFP
What are the treatment options for hepatocellular carcinoma?
Resection, liver transplant, radiofrequency ablation, chemotherapy
Palliative care in end-stage disease
