Liver Flashcards
Give a mneumonic for the surgical seive approach
V : vascular
I : infective
T : traumatic
A : autoimmune
M : metabolic
I : inflammatory
N : neoplastic
Give 4 causes of acute liver failure
- Paracetamol overdose
- Alcohol
- Viral hepatitis (usually A or B)
- Acute fatty liver of pregnancy
What are the features of acute liver failure ?
- Jaundice
- Coagulopathy: raised prothrombin time
- Hypoalbuminaemia
- Hepatic encephalopathy
- Renal failure is common (‘hepatorenal syndrome’)
what are the 3 stepwise stages of alcoholic liver disease
- Alcoholic fatty liver (hepatic steatosis)
- Alcoholic hepatitis
- Cirrhosis
what can be seen histologically in alcoholic hepatitis ?
Mallory bodies
Give 7 findings that suggest alcoholic fatty liver disease has progressed to alcoholic hepatitis
- Painful hepatomegaly
- Neutrophic leukocytosis
- Raised AST and ALT with AST/ALT ratio 2:1.
- Raised ALP
- Raised GGT
- Thrombocytopenia
- Hypoglycaemia
What can be used to treat alcoholic hepatitis ?
- Abstinence
- Glucocorticoids (e.g. prednisolone)
What is seen on bloods once chronic alcohol use has caused cirrhosis ?
Raised bilirubin
How do you calculate the units in an alcoholic drink?
multiply the number of millilitres by the ABV and divide by 1,000
Explain the different symptoms of alcohol withdrawwal experienced at different times
- 6-12 hours: tremor, sweating, headache, craving and anxiety
- 12-24 hours: hallucinations
- 24-48 hours: seizures
- 24-72 hours: delirium tremens
What is used to treat alochol withdrawal ?
Chlordiazepoxide
- Orally
- Reducing regime
- Reduced over 5-7 days.
what does excessive alcohol use cause a deficiency of
Thiamine (B1)
what can thiamine deficiency lead to and how is this prevented ?
- Wernicke’s encephalopathy and Korsakoff syndrome.
- IM or IV pabrinex (high dose B vitamins)
what is seen in wernicke’s encephalopathy ?
- Altered mental state (e.g. confusion)
- Nystagmus
- Opthalmoplegia
- Ataxia
what is seen in korsakoffs syndrome ?
- Memory impairment
- Behavioural changes
- Confabulation
what are the stages of non alcoholic fatty liver disease
- Non-alcoholic fatty liver disease
- Non-alcoholic steatohepatitis (NASH)
- Fibrosis
- Cirrhosis
what are the RF for NAFLD
- Obesity
- T2DM
- Hyperlipidaemia
- HTN
- Smoking
what is found on bloods and examination to first suggest NAFLD
- Examination : hepatomegaly
- Bloods : Raised ALT
Usually asymptomatic
what is used to confirm a fatty liver in NAFLD ?
- Liver USS
- Shows increased echogenicity
what is the first line investigation for assessing fibrosis in somebody with NAFLD?
- Enhanced liver fibrosis (ELF) blood test
- 10.51 or above – advanced fibrosis
- Under 10.51 – unlikely advanced fibrosis (NICE recommend rechecking every 3 years in NAFLD)
What does the ELF measure ?
Three markers (HA, PIIINP and TIMP-1)
Once the ELF has confirm advanced fiborsis what is done to assess cirrhosis ?
- Transient elastography (“FibroScan’)
If symptomatic, how dose viral hepatitis present
- Painful hepatomegaly
- Fatigue
- Flu-like illness
- Pruritus
- N&V
- Muscle joints and aches
- Jaundice
- Dark urine
What are the signs of viral hepatitis ?
- Raised AST & ALT with»_space;»ALT.
- Rise in bilirubin = jaundice
- Atypical lymphocytosis
Hepatitis A - type, transmission, vaccine, presentation, diagnosis, treatment, can it cause chronic hepatitis ?
- RNA
- Faecal-oral (usually contaminated water)
- +ve vaccine
- Presentation : flue like prodrome, RUQ pain, tender hepatomegaly jaundice, derrangved LFTs
- IgM antibodies for diagnosis = active infection.
- Supportive
- Does NOT cause chronic disease.
Hepatitis B - type, transmission, presentation, vaccine, management, can it cause chronic hepatitis ?
- DNA
- Blood / bodily fluids
- fever, jaudince and elevated transaminases
- +ve vaccine
- Supportive / antivirals
- 5-15% develop chronic disease
what hepatitis b serology would suggest previous vaccination?
Anti-HBs positive but all other serology negative
What hepatitis B serology suggest active infection ?
- HBsAg -> surface antigen (either acute or chronic if present >6mnths)
If active hepatitis infection, what further testing is perfomed
- E antigen (HBeAg) : marker of viral replication and implies high infectivity
- Hepatitis B virus DNA (HBV DNA) : direct count of viral load
what is used to distinguish acute, chronic and past infections ?
- Core antibodies (HBcAb)
Explain how core antibodies distinguish between acute, chronic and past infections
- Acute : IgM high titre
- Chronic : IgM low titre
- Past : IgG core antibodies but HBsAg is negative
Give 6 complications of hepatitis B
- Chronic hepatitis : ‘ground glass’ hepatocytes on light microscopy.
- Fulminant liver failure
- Hepatocellular carcinoma
- Glomerulonephritis
- Polyarteritis nodosa
- Cryoglobulinaemia
Hepatitis C - type, transmission, vaccine, treatment, can it cause chronic hepatitis ?
- RNA
- Blood and body fluids
- No vaccine
- Treated with direct acting antiviral (sofosbuvir, daclatasir).
- Majority will develop chronic hepatitis without treatment
Testing for acute hep C infection
- Hepatitis C RNA
Give 2 important complications of chronic hepatitis C
- Liver cirrhosis
- Hepatocellular carcinoma
Hepatitis D - type, diagnosis, treatment
ONLY EXISTS ALONGSIDE HEPATITIS B
- RNA
- PCR reaction of hepatitis D RNA
- Treatment : pegylated interferon alpha
Hepatitis E : type, transmission, vaccine and can it cause chronic hepatitis ?
- RNA
- Faecal-oral route
- No vaccine
- Does not cause chronic disease
Who is affected by type I autoimmune hepatitis ?
- Both adults and children
- Mainly older women, after menopause
Who is affected by Type II autoimmune hepatitis
- Children only
- Girls > boys
What antibodies are seen in type I autoimmune hepatitis ?
- Anti-nuclear (ANA)
- Anti-smooth muscle (anti-actin)
what antibodies are seen in type II autoimmune hepatitis ?
- Anti-liver/kidney microsomeal type I antibodiers (anti-LKM-1)
what is seen on liver biopsy in autoimmune hepatitis ?
- Inflammation extending beyond the limiting plate “piecemeal necrosis’
- Bridging necrosis
How will autoimmune hepatitis type II present in a question
Children, acute hepatitis (fever, jaudice) with high transaminases and jaundice
How is autoimmune hepatitis managed ?
- High dose steroids (prednisolone)
- Immunosuppressants (e.g. azathioprine)
- Liver transplant in end stage liver disease
what is ischaemic hepatitis
- Diffuse hepatic injury following hypoperfusion.
- Usually an inciting event (e.g. cardiac arrest) followed by marked increases in aminotransferase levels
Give the 4 most common causes of liver cirrhosis
- Alcohol-related liver disease
- NAFLD
- Hepatitis B
- Hepatitis C
What would be seen on an USS in liver cirrhosis
- Nodularity of the surface
- Corkscrew appearance to hepatic arteries
- Enlarged portal vein with reduced flow
- Ascites
- Splenomegaly
How are complications of liver cirrhosis monitored ?
- MELD every 6mnths
- Endoscopy for varices every 3 years
- USS and alpha-fetoprotein every 6 mnths for hepatocellular carcinoma
What scoring system is used every 6 mnths in those with compensated liver cirrhosis and what does it look at ?
- MELD score
- Bilirubin, creatinine , INR and sodium
- Gives estimated 3-mnth mortality as a percentage
what score uses 5 factors to assess severity of cirrhosis and prognosis and what are they ?
- Child-Pugh score
ABCDE - A : Albumin
- B : Bilirubin
- C : Clotting (INR)
- D : Dilation (ascites)
- E : Encephalopathy
<7 = A, 7-9 = B, >9 = C
When is liver transplantation considered in those with liver cirrhosis
When there are signs of decompensation
A : ascites
H : hepatic encephalopathy
O : Oesophageal varices bleeding
Y : yellow (jaundice)
Give 6 important complications of liver cirrhosis
- Malnutrition and muscle wasting
- Portal hypertension and oesophageal varices (+/- bleeding).
- Ascites and spontaneous bacterial peritonitis
- Hepatorenal syndrome
- Hepatic encephalopathy
- Hepatocellular carcinoma
Why does liver cirrhosis result in portal hypertension and varices
- Liver cirrhosis increases resistance to blood flow from the portal vein
- This increases back pressure on the portal system = portal hypertension
- This causes veins to swell at sites where collaterals form.
If identified on endoscopy, what is done to prevent varices bleeding ?
- 1st line = propanolol
- EVL : endoscopic variceal band ligation
Explain the steps to managed variceal bleeding
- Call for help
- ABCDE
- Consider blood transfusion (active major haemorrhage protocol)
- Correct clotting : FFP
- Vasopressive agents (IV terlipressin)
- Prophylactic IV broad spec Abx
- Urgent endoscopy with variceal band ligation
what are two other options for uncontrolled bleeding in oesophageal varices ?
- Sengstaken-Blakemore tube
- Transjugular intrahepatic portosystemic shunt (TIPS) : connects hepatic vein to portal vein to relieve pressure on the portal system
Explain the blood flow to the liver
- 30% from the
common hepatic artery : celiac trunk at T12 branches into the common hepatic artery before forming the proper hepatic and then right and left hepatic arteries - 70% (deoxygenated) from the portal vein : formed from the splenic veins and the superior mesenteric veins
Fwhy does liver cirrhosis cause ascites ?
- The increased pressure in the portal system caused by the increased resistance to flow causes fluid to leak out of the capillaries in the liver and other abdo organs into the peritoneal cavity.
Give the 6 management options of ascites caused by liver cirrhosis
- Low sodium diet
- Aldosterone antagonists (spironolactone).
- Paracentesis
- Prophylactic Abx (ciproflaxacin) if <15g/litre of protein in ascitic fluid
- TIPS in refractory ascites
- Liver transplant in refractory ascites
What is spontaneous bacterial peritonitis ?
Form of peritonitis seen in patients with ascites caused by liver cirrhosis
what are the 3 features of SBP
- Ascites
- Fever
- Abdo pain
how is SBP diagnosed
- Paracentesis : neutrophil count >250cells/ul
- Most common E.coli, can be klebsiella pneumo niae
How is SBP managed
IV cefotaxime
what is hepatic encephalopathy
- Reduced brain function caused by a build-up of neurotoxic substances (e.g. ammonia)
Give the 4 stages of hepatic encephalopathy
- Grade I: Irritability
- Grade II: Confusion, inappropriate behaviour
- Grade III: Incoherent, restless
- Grade IV: Coma
What is the treatment of hepatic encephalopthy ?
- 1st line = lactulose (aimining for 2-3 soft stools daily)
- 2nd = Rifaximin (reduce no. of intestinal bacterial producing ammonia)
what is the most common primary liver cancer
Hepatocellular carcinoma
what is the main risk factor for hepatocellular carcinoma ?
- Liver cirrhosis, caused by :
- Hep B and C
- Alcohol related liver disease
- NAFLD
- Haemochromatosis
- PBC
what is the tumour marker for hepatocellular carcinoma and the first-line imaging
- Alpha-fetoprotein
- Liver USS
What is a cholangiocarcinoma, where is the most common site, biggest RF what is its tumour marker and how does it present ?
- Bile duct cancer
- Perihilar region
- RF = PSC
- CA19-9 is tumour marker
- Obstructive jaundice : pale stools, dark urine and generalised itching
- Biliary colic, anorexia, weight loss
what kind of disease is haemochromatosis and what chromosome does it affect
- Autosommal recessive causing iron overload
- Mutations in the HFE gene on both copies of chromosome 6
How does haemochromatosis present
- Usually >40, later in women due to menstruation eliminating iron
- Early : Chronic tiredness, Athralgia (hands) and ED
- Bronze skin pigmentation
- DM
- Liver : stigmata of disease, hepatomegaly, cirrhosis
Give 2 reversible complications of haemochromatosis
Cardiomyopahy
Skin pigmentation
Give 4 irreversible complications of haemochromatosis
- Liver cirrhosis
- DM
- Hypogonadotrophic hypogonadism
- Arthropathy
what are the initial investigations for haemochromatosis
- Ferritin (not usually abnormal in early stages)
- Transferrin saturation
what is the typical iron study in patients with haemochromatosis
- Transferrin saturation > 55% in men or > 50% in women
- Raised ferritin (e.g. > 500 ug/l) and iron
- Low TIBC
How is haemachromatosis managed >
- Venesection : initially weekly (transferrin saturation kept below 50% and ferritin below 50ug/l)
- Desferrioxamine can be used second line
Give 7 complications of haemochromatosis
- DM
- Liver cirrhosis
- Endocrine and sexual problems (hypogonadism, erectile dysfunction, amenorrhea and reduced fertility)
- Cardiomyopathy
- Hepatocellular carcinoma
- Hypothyroidism
- Chondrocalcinosis (calcium pyrophosphate deposits in joints) causes arthritis
what is wilson’s disease, wha chromosome is effected and when does it typically present ?
- AR + excess copper
- Wilsons disease protein (ATP7B) on chromosome 13
- 10-25 years
How does wilson’s disease present
- Liver : hepatitis, cirrhosis
- Neuro : parkinsonism, asterixis, chorea, dementia
- Kayser-Fleischer rings
- Haemolysis
- Renal tubular acidosis
- Blue nails
How is wilson’s disease diagnosed ?
- Screening : low serum caeruloplasmin
- Increased 24hr urinary copper excretion and reduced total serum copper
- The diagnosis is confirmed by genetic analysis of the ATP7B gene
- Slit lamp for kayser-fleischer rings
How is Wilson’s disease managed ?
- Copper chelation using penicillamine
- Trientine hydrochloride can be used second line
what is the importance of Alpha-1 antitrypsin ?
- Protease inhibitor
- Inhibits the action of neutrophil elastase which digests elastin
what is alpha-1 antitrypsin deficiency, whay chromsome is affected and how is it inherited ?
- Low levels of alpha-1 antitrypsin
- Chromosome 14
- Co-dominant inheritance
what 2 organs are affected by alpha-1 antitrypsin deficiency ?
- Lungs : causes bronchiectasis and emphysema
- Liver : cirrhosis and hepatocellular carcinoma in adults, cholestasis in children
how is A1AT deficiency diagnosed ?
- Low A1AT concentrations
- Genetic testing
- Spirometry : obstructive picture
What is seen on liver biopsy in A1AT deficiency ?
Periodic acid-Schiff positive staining globules in hepatocytes, resistant to diastase treatment
How is A1AT deficiency managed ?
- Stop smoking
- Symptomatic management : bronchodilators, physio
- IV A1AT protein concentrates
- Surgery : lung volume reduction surgery, transplant
what incisions may be seen in liver transplants ?
- Rooftop
- Mercedes Benz
Give 5 contraindications to liver transplantation
- Significant co-morbidities (e.g., severe kidney, lung or heart disease)
- Current illicit drug use
- Continuing alcohol misuse (generally 6 months of abstinence is required)
- Untreated HIV
- Current or previous cancer (except certain liver cancers)
Who is affected by PBC and where in the liver is affected ?
- Middle aged women 40-60
- Autoimmune condition causing inflammation of the intrahepatic bile ducts
Give 6 symptoms of PBC
- Fatigue
- Pruritus
- RUQ pain
- Jaundice
- Pale, greasy stools
- Dark urine
what is seen on examination in PBC
- Xanthoma and xanthelasma
- Excoriations
- Hepatosplenomegaly
- Clubbing
why does PBC cause itching, jaundice, pale stools and dark urine?
The inflammation of intrahepatic bile ducts causes obstruction. Bile acids can’t be excreted = itching. Bilirubin can’t be excreted = jaundice. Lack of bilirubin = pale stools. As it is excreted in urine = dark urine.
What is seen on LFTs in PBC
- Raised ALP
What autoantibodies are seen in PBC
- Anti-mitochondrial antibodies (AMA)
- raised IgM
What is given to slow disease progression in PBC?
- First-line: ursodeoxycholic acid
what else is used to managed PBC ?
- Pruritus: cholestyramine
- Fat-soluble vitamin supplementation
- Liver transplantation
e.g. if bilirubin > 100
what is the most crucial complication of PBC ?
- Liver cirrhosis and its complications
- Increased risk of hepatocellular carcinoma
- Osteomalacia and osteoporosis
What is primary sclerosing cholangitis
- There is inflammation of both the intra and extrahepatic bile ducts.
- This leads to strictures and the obstruction to flow of bile out of the liver.
- Thos eventually causes hepatitis, fibrosis and cirrhosis
Give 3 associations with PSC
- UC
- Crohns
- HIV
How does PSC present ?
- RUQ pain
- Pruritus
- Fatigue
- Jaundice
- Hepatomegaly
- Splenomegaly
What is seen on LFTs in PSC
Raised ALP
what is the diagnostic imaging for PSC
- Magnetic resonance cholangiopancreatography (MRCP)
- Will show multiple biliary strictures giving a ‘beaded appearance’
How is PSC managed ?
- Endoscopic retrograde cholangio-pancreatography (ERCP) may be used to treat dominant strictures
Give 2 important compications of PSC
- Cholangiocarcinoma
- Increased risk of colorectal cancer
What is the difference between IgG4-related sclerosing cholangitis and PSC
- Elevated IgG4 in the blood + it responds well to treatment with steroids unlike PSC
What does ascites with a SAAG of >11g/l suggested ?
Portal HTN
Most common cause of ascites with a SAAG of >11g/L
LIVER DISORDERS : cirrhosis, failure, mets
Other causes of ascites with a SAAG >11g/L
- Cardiac : right HF, constrictive pericarditis
- Budd-Chiari syndrome
- Portal vein thrombosis
- Veno-occlusive disease
- Myxoedema
Causes of ascites with a SAAG <11g/L
- Hypoalbuminaemia : nephrotic syndrome, severe malnutrition (e.g. Kwashiorkor)
- Malignancy : peritoneal carcinomatosis
- Infections : tuberculous peritonitis
- Other causes : pancreatitis, bowel obstruction, biliary ascites, postoperative lymphatic leak, serositis in connective tissue diseases
how to remember the key features of PBC
M rule
- IgM
- anti-Mitochondrial antibodies
- Middle aged females
What is alcoholic ketoacidosis
- Non diabetic euglycaemic ketoacidosis
How does alcoholic ketoacidosis present
Metabolic acidosis
Elevated anion gap
elevated serum ketone levels
Normal or low glucose concentration
How is alcoholic ketoacidosis managed ?
Infusion of saline and thiamine
In terms of screening for liver cirrhosis, when is a ‘Fibroscan’ offered
- Pts with hepatitis C
- M >50 units of alcohol a week, women >35 units and have done so for several mnths.
- Pts with alcohol-related liver disease
what further investigations are done in pts diagnosed with liver cirrhosis ?
- Upper GI endoscopy to assess for varices
- Liver USS (+/- alpha-feto protein) every 6 mnths to check for hepatocellular cancer
Who should be vaccinated against hep A
- People travelling to or going to reside in areas of high or intermediate prevalence, if aged > 1 year old
-People with chronic liver disease - Patients with haemophilia
- Men who have sex with men
- Injecting drug users
- Individuals at occupational risk
What is a common feature of autoimmune hepatitis type I
- Amenorrhoea
- Can present with signs of chronic liver disease
Presentation of acute fatty liver in pregnancy
Abdominal pain and itching followed by jaundice
When is activated charcoal given for a paracetamol overdose
Pt presents within 1 hour
When should acetylcysteine be given for paracetamol overdose regardless of paracetamol level ?
- Staggered overdose
- Doubt over time of ingestion
- Present after >24 hrs and clearly jaundiced, have hepatic tenderness or if ALT above upper limit of normal.
what medication can cause hyaline casts on urine microscopy ?
Furosemide
Presentation of carbon monoxide poisoning
- Severe headache
- N&V
- Vertigo
- Confusion
- Severe : flushed complexion, hyperpyrexia, arrhythmias
Diagnosis of carboxyhaemoglobin (CO2 poisoning)
Blood gas
When should acetylycystein be given if plasma-paracetamol level is not yet available
patients who present 8-24 hours after ingestion of an acute overdose of more than 150 mg/kg of paracetamol
Explain the grades of hepatic encephalopathy
I : Irritability
II : Confusion, inappropriate behaviour
III : Incoherent, restless
IV : coma
Advice in regards to alcohol intake
No more than 14 units of alcohol per week. If you do drink as much as 14 units per week, it is best to spread this evenly over 3 days or more’.
Have can pancreatic cancer present on LFTs ?
- Cholestatic picture
- Raised bilirubin, raised ALP, nomral ALT
what can be given to somebody exposed to hep B who is fully vaccinated and proven to have responded to vaccines ?
Give hepatitis B vaccine booster
what vaccines are CI in patients with HIV ?
LIve attenuated vaccines (e.g. BCG for TB, yellow fever, oral polio, intranasal influenza, varicella, MMR)
what are the features of foetal alcohol syndrome ?
- Microcephaly
- Smooth philtrum
- Hypoplastic upper lip and epicanthic folds
Blood result showing previous vaccine to hepatitis B
- HBsAg negative
- anti-HBs positive
- IgG anti-HBc negative
when should antibiotic prophylaxis be given to patients with ascites
- Previous SBP
- Fluid protein of <15g/l and either Child-Pugh of at least 9 or hepatorenal syndrome
5 features of hepatic encephalopathy
- Confusion (Reduced GCS)
- Asterixis
- Constitutional ataxia
- Triphasic slow waves on EEG
- Raised ammonia
Possible precipitating factors for hepatic encephalopathy
- Infection e.g. spontaneous bacterial peritonitis
- GI bleed
- Post transjugular intrahepatic portosystemic shunt
- Constipation
- Drugs: sedatives, diuretics
- Hypokalaemia
- Renal failure
what is associated with PBC
- Sjogren’s syndrome
- RA
- Systemic sclerosis
- Thyroid disease
what antibody might be positive in PSC ?
p-ANCA
What is Budd-Chiari syndrome ?
- Hepatic vein thrombosis
- Usually underlying haematological or procoagulant condition (e.g. anti-phospholipid syndrome)
Give 4 causes of Budd-Chiari syndrome
- Polycythaemia rubra vera
- Thrombophilia: activated protein C resistance, antithrombin III deficiency, protein C & S deficiencies
- Pregnancy
- COCP
Give the triad of Budd-Chiari syndrome
- Abdominal pain: sudden onset, severe
- Ascites → abdominal distension
- Tender hepatomegaly
Initial radiological investigation for Budd-Chiari
USS with Doppler flow studies
Name 3 drugs that can cause liver cirrhosis
methotrexate
methyldopa
amiodarone
What is Gilbert’s syndrome and in what fashion is it inherited ?
- Defective bilirubin conjugation due to deficiency of UDP glucuronosyltransferase
- Autosomal recessive
Features of Gilberts
- Unconjugated hyperbilirubinaemia (it won’t be seem in urine)
- Jaundice in intercurrent illness, exercise or fasting
Management of liver abscess
- percutaneous drainage
- antibiotics (Amoxicillin + ciprofloxacin + metronidazole)
- Penicillin allergic: ciprofloxacin + clindamycin
Common organisms in pyogenic liver abscess
- Children : staph aureus
- Adults : e.coli
What is the King’s college hospital criteria for consideration of liver transplant following paracetamol overdose
- pH <7.3, 24 hrs after ingestion !
OR
- All of the following :
Prothrombin time > 100 seconds
Creatinine > 300 µmol/L
Grade III or IV encephalopathy
Drugs that cause drug induced cholestasis (+/- hepatitis)
- COCP
- Antibiotics: flucloxacillin, co-amoxiclav, erythromycin
- Anabolic steroids, testosterones
- Phenothiazines: chlorpromazine, prochlorperazine
- Sulphonylureas
- Fibrates
Presentation of dengue fever
- High fever
- Severe muscle ache
- Widespread maculopapular rash
Blood presentation of dengue faver
- Thrombocytopenia
- Leukopenia
- Raised ALT
Presentation suggestive of alcoholic ketoacidosis
- Metabolic ketoacidosis
- Normal or LOW glucose
When do pts with ascites receive prophylactic ciprofloxacin ?
- Previous episode of SBP
- Fluid protein of <15 g/l AND either Child-Pugh score of at least 9 or hepatorenal syndrome