What is fulminant liver failure?
Rapid development of acute liver injury with severe impairment of synthetic function and hepatic encephalopathy in patient with obvious liver disease
Signs of portal hypertension, coagulopathy, hepatic encephalopathy
3wk prognosis
Give some differentials for acute isolated hepatomegaly.
- acute hepatitis (painful)
- hepatoadenocarcinoma (craggy liver)
- congestive hepatopathy (“nutmeg liver”) = liver dysfunction due to congestive heart failure; liver is speckled due to dilated, congested hepatic veins (if due to right heart failure = cardiac cirrhosis)
- schistosomiasis
- EBV
- CMV
- fatty liver
- liver cirrhosis (prior to portal hypertension)
What is alpha-fetoprotein?
Produced by yolk sac and liver during foetal development (foetal form of erum albumin)
Increased alpha-fetoprotein:
- omphocoele
- hepatocellular carcinoma
- neural tube defects
- non-seminomatous germ cell tumours
- yolk sac tumours
- ataxia telangiectasia
- germ cell tumours
- metastatic liver cancer
List the different autoimmune liver disease biomarkers.
- autoimmune hepatitis: IgG, smooth muscle antigen, anti-nuclear antibody (ANA), liver-kidney microsomal antigens
- primary biliary cirrhosis: anti-mitochondrial antibodies (AMA), IgM, ALP
- primary sclerosing cholangitis: 80% perinuclear anti-neutrophil cytoplasmic antibodies (pANCA), 20% ANA & SMA
Give some causes of unconjugated hyperbilirubinaemia.
Increased bilirubin production:
- haemolysis: ineffective erythropoiesis, resorption of haematomas, fulminant Wilson’s disease, etc.
- blood transfusion
Defective hepatic uptake/conjugation:
- congenital: Gilbert’s syndrome, Criggler-Najjar syndrome, physiological jaundice of the newborn, etc.
- acquired: drugs e.g. rifampicin
Give some causes of conjugated hyperbilirubinaemia.
Defective hepatic excretion of bilirubin
Congenital:
- Rotor’s syndrome
- Dubin-Johnson syndrome
Acquired:
- alcoholic hepatitis
- primary biliary cirrhosis
- acute liver failure
Where are the different aminotransferases found, and when are they released?
Release triggered by hepatocellular injury
AST = cytosolic & mitochondrial isoenzymes
- liver, heart, skeletal muscle, kidneys, brain, pancreas, lungs, leucocytes, RBCs
- less sensitive and specific to liver
ALT = cytosolic enzyme at highest conc. in liver
Give some causes of an increased AST/ALT ratio.
- non-alcoholic steatohepatitis (AST:ALT<1:1)
- alcohol (AST:ALT is at least 2:1 + increased gamma-GT)
- drugs: NSAIDs, Abx, statins, anti-epileptics, TB drugs, herbal, illicit
- glycogen storage disorders
- autoimmune hepatitis
- hep. B/C
Give some physiological and pathological causes of increased ALP.
Physiological:
- benign/familial
- 3rd trimester of pregnancy
- adolescents
Pathological:
- cholangiocyte damage
- bone disease
- metastatic liver disease
- adult bile ductopenia
- drug-induced cholestasis e.g. anabolic steroids
- primary sclerosing cholangitis
- primary biliary cirrhosis
- bile duct obstruction
Give some causes of increased gamma-GT.
- obesity
- MI
- diabetes
- COPD
- congestive heart failure
- alcoholism
- drugs e.g. carbamazepine, phenytoin, barbituates
- pancreatic disease
- hyperlipidaemia
- hepatobiliary disease
- prostate disease
- renal failure
- cholangiocyte damage
Give some causes of increased prothrombin time.
- consumptive coagulopathy (DIC)
- liver disease
- sepsis
- vit. K deficiency
- warfarin
- chronic cholestasis
Give some causes of ALT>10,000
Ischaemic acute hepatitis
Severe sepsis
Hypotension
Give some causes of ALT>5,000
Acute viral hepatitis
Jaundice
Hep. B&C
Give some causes of ALT 2.5x normal.
Non-alcoholic steatohepatitis
Autoimmune hepatitis
Chronic viral hepatitis
Drug reactions
What are some appropriate investigations in elevated ALT?
ACUTE:
- hep. A, B, C, E screen
- EBV, CMV, toxoplasmosis screen
- drugs screen
- Igs
- autoimmune profile
- caeruloplasmin
CHRONIC:
- thyroid function
- diabetes screen
- hep. B & C screen
- lipids
- Igs
- autoimmune profile
- ferritin
- caeruloplasmin
- alpha-1-antitrypsin
- TTG antibodies (coeliac disease)
What is de Morsier syndrome?
Septo-optic dysplasia
Congenital malformation syndrome
Underdeveloped optic nerve, pituitary gland dysfunction (causing obstructive jaundice), absence of septum pellucidum)
Give some causes of cirrhosis.
Alcohol Non-alcholic steatohepatitis Hep. B & C Alpha-1-antitrypsin deficiency Methotrexate
What are the main consequences in decompensated liver disease?
Ascites
Hepatic encephalopathy
Portal hypertension
What is the management of varices?
Prophylactic Abx
Resuscitation
Endoscopy = band ligation, sclerotherapy
Terlipressin (ADH analogue)
Balloon tamponade
Transjugular intrahepatic portosytemic shunt (TIPS)
