Hepatology: Liver failure, cirrhosis Flashcards
When is liver failure acute (hyperacute, acute and subacute)?
If onset of symptoms is in < 26 weeks in a patient with a previously healthy liver
1) Hyperacute = 7 days or less
2) Acute = 8-21 days
3) Subacute = 4-26 weeks
What is chronic liver failure?
Onset of liver failure on a background of cirrhosis
Which infections can cause liver failure?
1) Hepatitis A, B & E
2) CMV
3) Yellow fever
4) Leptospirosis
Which drugs can cause liver failure?
1) Paracetamol overdose
2) Halothane
3) Isoniazid
4) MDMA
5) Alcohol
Which two toxins can cause liver failure?
1) Amanita phalloides mushroom
2) Carbon tetrachloride
What are hepatic causes of liver failure?
1) Primary biliary cirrhosis
2) Non-alcoholic fatty liver disease
3) Autoimmune hepatitis
4) Malignancy
What are two pregnancy-related causes of liver failure?
1) Fatty liver of pregnancy
2) HELLP syndrome
What is a vascular cause of liver failure?
Budd-Chiari syndrome
What are genetic causes of liver failure?
1) Haemochromatosis
2) Wilson’s disease
3) Alpha-1 antitrypsin deficiency
What are the clinical features of liver failure?
1) Jaundice
2) Ascites
3) Abnormal bleeding
4) Hepatic encephalopathy
What is a complication of hepatic encephalopathy?
If cerebral oedema is severe, raised ICP may develop - more common in fulminant hepatic failure and has a high mortality rate
What does the presence of signs of both liver failure and chronic liver disease indicate?
A decompensation of chronic liver disease
How does hepatic encephalopathy develop?
1) In liver failure, nitrogenous waste (ammonia) accumulates in the circulation
2) This can cross the BBB and once in cerebral circulation it is detoxified by astrocytes which form glutamine through the amidation of glutamate
3) The excess glutamine disrupts the osmotic balance and the astrocytes begin to swell, giving rise to cerebral oedema
What are the four stages of hepatic encephalopathy?
1) Altered mood and behaviour, disturbance of sleep pattern and dyspraxia
2) Drowsiness, confusion, slurring of speech and personality change
3) Incoherency, restlessness, asterixis
4) Coma
What are you looking for in clinical examination of liver failure?
Signs of encephalopathy and chronic liver disease
What investigations are done in liver failure?
1) Blood tests
2) Peritoneal tap for microscopy and culture
3) Abdominal ultrasound
Which blood tests are done in liver failure?
FBC, U&E, CRP, LFT, albumin, clotting screen (INR)
When is a peritoneal tap done in liver failure?
If there is ascites - to look for spontaneous bacterial peritonitis
Why is an INR done in liver failure?
To look for coagulopathy and establish a diagnosis of liver failure
What are you looking for in a FBC in liver failure?
1) Leucocytosis - possible infective cause
2) Thrombocytopenia - in chronic liver disease
3) Anaemia - normocytic could indicate haemolytic anaemia as in Wilson’s or a GI bleed from oesophageal varices, macrocytic could indicate B12 and folate deficiency as in alcohol excess
Why are U&Es done in liver failure?
1) To establish baseline renal function
2) To look for hepato-renal syndrome
3) To look for any electrolyte abnormalities e.g. hypokalaemia which can worsen encephalopathy and should be corrected
What other blood tests can be done in liver failure to determine the cause?
1) Paracetamol level
2) Hepatitis
3) EBV
4) CMV serology
5) Iron studies (haemochromatosis)
6) α-1 anti-trypsin
7) Caeruloplasmin level (Wilson’s disease)
8) Auto-antibodies (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis)
What is the most common complication of acute liver failure?
Infection - bacterial infection occurs in up to 80% of patients, fungal infection in 30%
Why does infection occur as a complication of acute liver failure?
Decrease phagocyte action, reduced complement levels and multiple invasive medical interventions
How do patients with infection as a complication of acute liver failure present?
Often atypically with no fever or raised WCC
What are other complications of acute liver failure?
1) Cerebral oedema ± raised ICP
2) Bleeding (where there is a source e.g. introduction of ICP monitors)
3) Hypoglycaemia (easily treated with glucose)
4) Multi-organ failure
What are major complications of cirrhosis?
1) Ascites
2) Spontaneous bacterial peritonitis
3) Hepatic encephalopathy
4) Portal hypertension
5) Variceal bleeding
6) Hepatorenal syndrome
How is liver failure managed?
1) Treat the underlying cause if possible
2) Monitor observations closely including blood glucose
3) Liver transplantation may be necessary
How is hepatic encephalopathy managed?
1) Lactulose - to help nitrogenous waste loss through the bowels, reducing encephalopathy
2) IV mannitol (osmotic diuretic) - to reduce cerebral oedema
How is coagulopathy in liver failure treated?
1) Vitamin K - helps production of coagulation factors
2) Fresh frozen plasma - if patient is bleeding
How is spontaneous bacterial peritonitis managed?
1) Broad spectrum antibiotics
2) Prophylactic ciprofloxacin if high risk e.g. previous episodes, low albumin, high INR and low ascitic albumin
How is renal dysfunction in liver failure treated?
1) May require haemofiltration
2) If patient required fluid resuscitation, human albumin solution rather than crystalloid fluid
What are the KCH criteria for liver transplant?
They are designed to predict poor outcome in acute liver failure and are an indication of patients that should be considered for urgent liver transplantation
What are the KCH criteria for liver transplant for paracetamol induced liver failure?
1) Arterial pH < 7.3 24h after ingestion OR
2) Pro-thrombin time > 100s AND creatinine > 300 µmol/L AND grade III or IV encephalopathy
What are the KCH criteria for liver transplant for non-paracetamol induced liver failure?
1) Prothrombin time > 100s OR
2) Any three of:
- Drug induced liver failure
- Age < 10 or > 40 years
- 1 week from 1st jaundice to encephalopathy
- Prothrombin time > 50s
- Bilirubin ≥ 300µmol/L
Which drug can be used in patients with ascites to aid with offloading the additional fluid?
Spironolactone
Which drugs are used to prevent/reduce recurrence of overt hepatic encephalopathy?
1) Rifaximin - antibiotic that reduces intestinal absorption of ammonia, resulting in a delay in the occurrence of acute episodes of hepatic encephalopathy
2) Lactulose - can also be used in the community to prevent episodes of hepatic encephalopathy
What is cirrhosis?
Diffuse fibrosis and structural abnormality of the liver, characteristic of chronic liver disease
What is the definition of compensated liver cirrhosis?
Where sufficient liver function remains to keep the patient systemically well
What are the clinical features of compensated cirrhosis?
1) Fatigue + anergia
2) Anorexia/cachexia
3) Nausea ± abdo pain
4) Spider naevi
5) Gynaecomastia
What are the additional symptoms in decompensated cirrhosis?
1) Ascites
2) Oedema
3) Jaundice
4) Pruritis
5) Palmar erythema
6) Gynaecomastia ± testicular atrophy
7) Easy bruising
What are the most common causes of cirrhosis?
1) Alcohol
2) Hepatitis B + C
2) NAFLD
What are the autoimmune causes of cirrhosis?
1) Autoimmune hepatitis
2) Primary biliary cholangitis
3) Primary sclerosing cholangitis
4) Sarcoid
What are genetic causes of cirrhosis?
1) Haemochromatosis
2) Wilson’s disease
3) Alpha-1 antitrypsin deficiency
What drugs can cause liver cirrhosis?
1) Methotrexate
2) Amiodarone
3) Isoniazid
What are other rarer causes of cirrhosis?
1) Budd-Chiari syndrome
2) Heart failure
3) Tertiary syphilis
What initial blood tests should be done for cirrhosis?
1) LFTs (AST, ALT, ALP, GGT, albumin, bilirubin)
2) FBC
3) U&Es
4) INR
5) Tests to help determine cause
What are you looking for on FBC in cirrhosis?
1) Leucocytosis - possible infective cause
2) Thrombocytopenia - in chronic liver disease
3) Anaemia
What could normocytic anaemia in cirrhosis indicate?
Haemolytic anaemia e.g. in Wilson’s disease or a GI bleed from oesophageal varices
What could a macrocytic anaemia in cirrhosis indicate?
B12 and folate deficiency e.g. in alcohol excess
Why do you do U&Es in cirrhosis?
1) To establish baseline renal function
2) Look for hepato-renal syndrome
3) Look for any electrolyte abnormalities - which can worsen encephalopathy and should be corrected
Why do you do INR in cirrhosis?
To look for coagulopathy - helps define the severity of cirrhosis
Which specific blood tests do you do in cirrhosis do determine the cause?
1) Hepatitis
2) CMW serology
3) Iron studies (haemochromatosis)
4) α-1 anti-trypsin (α-1 antitrypsin deficiency)
5) Caeruloplasmin level (Wilson’s disease)
6) Iron studies (hereditary haemochromatosis)
7) Auto-antibodies (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis)
What investigation do you do in cirrhosis if ascites is present?
Peritoneal tap for MC&S - to look for spontaneous bacterial peritonitis
Why do you do a peritoneal tap if there is ascites?
To check for spontaneous bacterial peritonitis
What investigation can be done to identify Budd-Chiari syndrome?
Doppler ultrasound
What investigation is used to diagnose NAFLD?
Transient elastography (or acoustic radiation force impulse imaging)
What is the final investigation that can be done to confirm the underlying diagnosis of cirrhosis if still in doubt?
Liver biopsy
What score is used to estimate the severity of liver cirrhosis?
Child-Pugh score
What is the Child-Pugh score used for?
Predictor of mortality + may be used to predict the need of liver transplant
How is the degree of cirrhosis defined used the Child-Pugh score?
1) Child-Pugh A = < 7 points
2) Child-Pugh B = 7-9 points
3) Child-Pugh C = > 9 points
What are the components of the Child-Pugh score?
1) Bilirubin
2) Albumin
3) Prothrombin time (seconds prolonged)
4) Encephalopathy
5) Ascites
What are the complications of liver cirrhosis?
1) Ascites
2) Spontaneous bacterial peritonitis (SBP)
3) Liver failure
4) Hepatocellular carcinoma
5) Lower oesophageal varices ± haemorrhage
6) Renal failure
What causes ascites in cirrhosis?
Portal hypertension + hypoalbuminaemia
What is a complication of ascites?
Spontaneous bacterial peritonitis
How does SBP present?
1) Sudden onset
2) May present atypically with no abdominal tenderness or guarding
When should SBP be suspected?
Patients with cirrhosis and ascites who deteriorate suddenly with no other obvious cause
How is SBP diagnosed?
Ascitic tap with neutrophils > 250 mm3
Which patients are particularly at risk of SBP and should be treated with prophylactic antibiotics e.g. ciprofloxacin?
Patients with low ascitic albumin
Which antibiotic is used as prophylaxis for SBP?
Ciprofloxacin
What are complications of liver failure which has progressed from cirrhosis?
Hepatic encephalopathy + coagulopathy
What is the complication of hepatic encephalopathy?
Cerebral oedema progressing to raised ICP + death
What is a complication of coagulopathy?
Life-threatening bleeds in those with a source of bleeding
What are patients with cirrhosis (esp. those with hepatitis B and C) and a significantly increased risk for?
Hepatocellular carcinoma
What causes oesophageal varices ± haemorrhage in cirrhosis?
1) The development of portal hypertension in cirrhosis leads to dilatation of oesophageal veins
2) These are liable to rupture - can be fatal esp. in patients with coagulopathy
What is hepatorenal syndrome?
Cirrhosis + ascites + renal failure (if other causes of AKI have been ruled out)
What causes renal failure in cirrhosis?
Abnormal haemodynamics in liver disease cause renal vasoconstriction which makes the kidneys more susceptible to injury (v poor prognosis)
What is the overall management principle for decompensated liver cirrhosis?
There are many sequelae of decompensated liver disease which require careful management by a MDT
What is conservative management in decompensated liver cirrhosis?
Good nutrition with total alcohol abstinence
Which drugs should be avoided in decompensated liver cirrhosis?
NSAIDs, sedatives + opioids
How are patients with cirrhosis screened for hepatocellular carcinoma?
Ultrasound scan + serum AFP every 6 months
What can be used to manage pruritis in decompensated liver cirrhosis?
Cholestyramine (bild acid sequestrant)
How is ascites managed in decompensated liver cirrhosis?
1) Fluid restriction - < 1.5L per day
2) Low salt diet
3) Spironolactone ± furosemide if necessary
4) Severe cases - therapeutic paracentesis + albumin infusions
How is ascites conservatively managed in decompensated liver cirrhosis?
Fluid restriction (< 1.5L/day) + low salt diet
What is the first line diuretic for ascites in decompensated liver cirrhosis?
Spironolactone (furosemide added if necessary)
How are severe cases of ascites in decompensated liver cirrhosis managed?
Therapeutic paracentesis + albumin infusions
How can recurrent episodes of hepatic encephalopathy be reduced in frequency in decompensated liver cirrhosis?
Prophylactic lactulose + rifaximin
What are risk factors making patients high risk for SBP?
1) Previous episodes of SBP
2) Low albumin
3) High INR
4) Low ascitic albumin
What is the ultimate, definitive treatment for decompensated liver cirrhosis?
Liver transplant
What scores can be used to help predict severity of chronic liver disease?
Model for End-stage Liver Disease (MELD) and UK End-stage Liver Disease (UKELD)
When are KCH criteria used?
In acute (or acute on chronic) liver failure where a decision needs to be made rapidly (generally not used for chronic cases)
