Hepatology - Presenting problems in liver disease Flashcards
What is acute liver failure?
This is a rare condition in which hepatic encephalopathy results from a sudden impairment of hepatic function. In a patient whose liver was previously normal, the level of injury needed to cause liver failure is very high. In those with pre-existing chronic liver disease, the additional acute insult needed is much less. Although a liver biopsy may be useful, it is the presence or absence of features suggestive of chronic liver disease that helps. Acute viral hepatitis is the most common cause worldwide, with paracetamol toxicity most common in the UK. Acute liver failure can occur occasionally from other drugs, mushroom poisoning, pregnancy, Wilson’s disease or following shock, alcohol and sepsis.
How should acute liver failure be assessed?
Hepatic encephalopathy is THE cardinal feature of acute liver failure. It starts with mild, episodic reduced concentration and alertness, progressing to restlessness, aggressive outbursts, drowsiness and coma. Cerebral oedema may cause increased ICP leading to unequal or abnormally reacting pupils, fixed pupils, hypertensive episodes, bradycardia, hypoventilation, profuse sweating, myoclonus or decerebrate posturing. Papilloedema is a rare sign and occurs late.
Examination shows jaundice which develops rapidly, but is absent in Reye’s syndrome and death occasionally occurs in fulminant acute liver failure before jaundice develops. Hepatomegaly is unusual; if found with sudden onset ascites it suggests venous outflow obstruction (Budd-Chiari syndrome). Splenomegaly is uncommon.
How is acute liver failure classified?
Hyperacute = <7 days, cerebral oedema
- usually viral or paracetamol poisoning
Acute = 8-28 days, cerebral oedema
- cryptogenic or drugs
Subacute = 29 days to 12 wks, oedema uncommon
- cryptogenic or drugs
What investigations should be performed to determine the underlying cause of acute liver failure?
Toxicology screen - blood and urine IgM anti- HBc, HBsAg IgM anti-HAV Anti-HEV, HCV, CMV, HSV, EBV serology Caeruloplasmin, serum copper, urinary copper, slit lamp eye examination Autoantibodies: ANF, ASMA, LKM, SLA Immunoglobulins USS of liver and Doppler of hepatic veins
PT quickly becomes prolonged as coagulation factor synthesis fails, and is an extremely useful test that should be performed twice daily. Plasma aminotransferase activity rises to 100-500 times normal after paracetamol OD, but falls as liver damage progresses and is not helpful in determining progress. Child Pugh score is most helpful in acute liver disease.
What adverse prognostic factors are associated with acute liver failure?
Paracetamol OD:
- pH <7.3 at or beyond 24 hrs following OD, or
- serum creatinine >300 + PT > 100secs + encephalopathy grade 3 or 4
Non paracetamol OD:
- PT > 100secs, or
- factor V level <15% and encephalopathy grade 3 or 4, or
- any 3 of: bilirubin > 300; PT >50secs; jaundice to encephalopathy time > 7 days; age <10 or >40
How should acute liver failure be managed?
Treat patient on HDU or ITU as soon as progressive prolongation of PT or hepatic encephalopathy is identified, so that prompt treatment of complications (hypoglycaemia, infections, renal failure, metabolic acidosis) can be performed. Treatment is supportive. NAC in paracetamol poisoning, liver transplantation is an option depending on prognosis. 1 year survival is around 60%.
How should an isolated increase in serum bilirubin be investigated?
Check conjugated bilirubin and exclude haemolysis. If these come back normal then reassure the patient. The likely cause is Gilberts syndrome.
How should a patient with a raised GGT be investigated further?
Consider:
- NAFLD/ incr. BMI - stage disease/ diet and exercise
- Drug toxicity - review current medication
- Alcohol excess - alcohol abstinence
A patient is found to have ALP (or transaminases) raised <2 x normal. Do they need further investigation?
Yes.
Take an alcohol history and recommend alcohol abstinence if appropriate. Stop hepatotoxic drugs, weight loss if BMI >25 and re check LFTs in 3-6 months.
If the LFTs are persistently abnormal then screen for chronic liver disease.
How should a patient with ALP/ transaminases raised >2 x normal be investigated further?
Screen for chronic liver disease:
- history
- USS
- HBsAg, HCVAb
- alpha 1 anti-trypsin
- autoimmune profile
- ferritin, caeruloplasmin
- immunoglobulins
On USS, if there are dilated bile ducts then consider MRCP or ERCP. If there aren’t any then arrange a liver biopsy to determine underlying cause.
When can jaundice be detected?
Jaundice is usually detected clinically when the plasma bilirubin exceeds 40umol/L.
Outline how bilirubin is metabolised?
Bilirubin in the blood is almost always all unconjugated and, because it is not water soluble, it is bound to albumin and does not enter the urine. Unconjugated bilirubin is conjugated by glucuronyl transferase into water soluble conjugates, which are exported into the bile.
Colonic bacteria convert conjugated bilirubin into stercobilinogen in the large intestine. A portion of this is lost to the stool in the form of stercobilin. Some of the stercobilinogen is reabsorbed in the blood as urobilinogen which can undergo enterohepatic circulation or be excreted in the kidneys are urobilinogen.
What are the causes of pre-hepatic jaundice?
This is caused by either haemolysis or by congenital hyperbilirubinaemia, and is characterised by an isolated raised bilirubin level. In haemolysis, destruction of red blood cells or their marrow precursors causes increased bilirubin production. Jaundice due to haemolysis is usually mild because a healthy liver can excrete a bilirubin load six times greater than normal before unconjugated bilirubin accumulates in the plasma. This does not apply to new borns. Gilbert’s syndrome is the only common form of non-haemolytic hyperbilirubinaemia. It is a familial autosomal dominant mutation that reduces expression of 5” UDP glucuronyl transferase. This decreases bilirubin conjugation and causes isolated accumulation of unconjugated bilirubin in the blood. It needs no treatment.
What causes hepatocellular jaundice?
Results from an inability of the liver to transport bilirubin into the bile, as a consequence of liver disease. In hepatocellular jaundice, the concentrations of BOTH unconjugated and conjugated bilirubin in the blood increase, perhaps because of the variable way in which bilirubin transport is disturbed. Parenchymal disease causing jaundice, usually also elevates transaminase levels. Acute jaundice with an alanine aminotransferase >1000 suggests hepatitis A or B, drug toxicity or hepatic ischaemia. USS and biopsy are frequently needed for precise diagnosis.
What causes obstructive or cholestatic jaundice?
Cholestatic jaundice may be caused by:
i) Failure of hepatocytes to initiate bile flow
ii) Obstruction of the bile ducts or portal tracts
iii) Obstruction of bile flow in the extrahepatic bile ducts between the porta hepatis and the ampulla of Vater
Without treatment cholestatic jaundice tends to progress because conjugated bilirubin is unable to enter the bile canaliculi and passes back into the blood, and also because there is failure of clearance of unconjugated bilirubin arriving at liver cells.
Abdominal pain suggests choledocholithiasis, pancreatitis or choledochal cyst. Jaundice is progressive in cancer and fluctuating in sclerosing cholangitis, pancreatitis and stricture.
